Marco 2

CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care
Identification, Evaluation, and

Management of Children With Autism
Spectrum Disorder
Susan L. Hyman, MD, FAAP,a Susan E. Levy, MD, MPH, FAAP,b Scott M. Myers, MD, FAAP,c COUNCIL ON CHILDREN WITH DISABILITIES,
SECTION ON DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder abstract

with reported prevalence in the United States of 1 in 59 children
(approximately 1.7%). Core deficits are identified in 2 domains: social a
Golisano Children’s Hospital, University of Rochester, Rochester, New
York; bChildren’s Hospital of Philadelphia, Philadelphia, Pennsylvania;
communication/interaction and restrictive, repetitive patterns of behavior. and cGeisinger Autism & Developmental Medicine Institute, Danville,
Children and youth with ASD have service needs in behavioral, educational, Pennsylvania
health, leisure, family support, and other areas. Standardized screening for
Clinical reports from the American Academy of Pediatrics benefit from
ASD at 18 and 24 months of age with ongoing developmental surveillance expertise and resources of liaisons and internal (AAP) and external
reviewers. However, clinical reports from the American Academy of
continues to be recommended in primary care (although it may be performed Pediatrics may not reflect the views of the liaisons or the
in other settings), because ASD is common, can be diagnosed as young as organizations or government agencies that they represent.
18 months of age, and has evidenced-based interventions that may improve Drs Hyman, Levy, and Myers all participated in development of the
outline of material to be covered, generation of content, and editing of
function. More accurate and culturally sensitive screening approaches are the document; and all authors approved the final manuscript as
needed. Primary care providers should be familiar with the diagnostic criteria submitted.
for ASD, appropriate etiologic evaluation, and co-occurring medical and The guidance in this report does not indicate an exclusive course of
treatment or serve as a standard of medical care. Variations, taking
behavioral conditions (such as disorders of sleep and feeding, gastrointestinal into account individual circumstances, may be appropriate.
tract symptoms, obesity, seizures, attention-deficit/hyperactivity disorder,
All clinical reports from the American Academy of Pediatrics
anxiety, and wandering) that affect the child’s function and quality of life. There automatically expire 5 years after publication unless reaffirmed,
revised, or retired at or before that time.
is an increasing evidence base to support behavioral and other interventions
to address specific skills and symptoms. Shared decision making calls for This document is copyrighted and is property of the American
Academy of Pediatrics and its Board of Directors. All authors have filed
collaboration with families in evaluation and choice of interventions. This conflict of interest statements with the American Academy of
Pediatrics. Any conflicts have been resolved through a process
single clinical report updates the 2007 American Academy of Pediatrics approved by the Board of Directors. The American Academy of
clinical reports on the evaluation and treatment of ASD in one publication with Pediatrics has neither solicited nor accepted any commercial
involvement in the development of the content of this publication.
an online table of contents and section view available through the American
DOI: https://doi.org/10.1542/peds.2019-3447
Academy of Pediatrics Gateway to help the reader identify topic areas within
the report. Address correspondence to Susan L. Hyman. E-mail: susan_hyman@
urmc.rochester.edu
To cite: Hyman SL, Levy SE, Myers SM, AAP COUNCIL ON

CHILDREN WITH DISABILITIES, SECTION ON DEVELOPMENTAL
INTRODUCTION AND BEHAVIORAL PEDIATRICS. Identification, Evaluation, and
Management of Children With Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a category of neurodevelopmental
Pediatrics. 2020;145(1):e20193447
disorders characterized by social and communication impairment and
Downloaded from www.aappublications.org/news by guest on June 19, 2020

PEDIATRICS Volume 145, number 1, January 2020:e20193447 FROM THE AMERICAN ACADEMY OF PEDIATRICS
restricted or repetitive behaviors.1 criteria after publication of the in children at different ages. What is
ASD affects more than 5 million Diagnostic and Statistical Manual of reported is age at recognition of
Americans, with an estimated Mental Disorders, Fifth Edition (DSM- symptoms, not the actual onset. As
prevalence of approximately 1.7% in 5)1 in 2013. The DSM-5 established a result, prevalence is more typically
children.2 The care needs of children a single category of ASD to replace reported than incidence, reflecting
with ASD are significant, affect the subtypes of autistic disorder, rates of ASD in the population at
parents and siblings as well, and Asperger syndrome, and pervasive a point in time.
require substantial community developmental disorder not
The reported prevalence of children
resources. Direct and indirect costs of otherwise specified in the Diagnostic
with ASD has increased over time,
caring for children and adults with and Statistical Manual of Mental
and primary care providers are often
ASD in the United States in 2015 were Disorders, Fourth Edition, Text
asked about the reasons for this
estimated to be $268 billion, more Revision (DSM-IV-TR). With the
increase. This increase may be
than the cost of stroke and current reported prevalence rate of 1:
attributable to several factors,
hypertension combined.3 The lifetime 59 children (approximately 1.7%), all
including broadening in the
cost of education, health, and other primary care providers can expect to
diagnostic criteria with ongoing
service needs for an individual with have children and youth with ASD in
revisions of the Diagnostic and
ASD ranges from $1.4 to $2.4 million their practices.2 As noted in earlier
Statistical Manual of Mental Disorders
dollars, depending on whether he or clinical reports, the primary care
(DSM), the more inclusive definition
she has any co-occurring intellectual provider has critical access to the
of pervasive developmental disorder
disabilities.4 To deliver timely and child in the context of the medical
with the adoption of the Diagnostic
effective medical, behavioral, home to identify symptoms of ASD
and Statistical Manual of Mental
educational, and social services early in childhood, support the family
Disorders, Fourth Edition (DSM-IV) in
across the lifespan means that through the process of diagnosis and
1994,8 increased public awareness of
primary care providers must intervention, address etiologic
the disorder and its symptoms,
understand the needs of individuals evaluations, help the family
recommendations for universal
with ASD and their families. ASD is understand how to interpret the
screening for ASD,5,9 and increased
more commonly diagnosed now than evidence supporting different
availability of early intervention and
in the past, and the significant health, interventions so they can effectively
school-based services for children
educational, and social needs of engage in shared decision-making,
with ASD. In part, the increasing
individuals with ASD and their and manage co-occurring medical
numbers of children with a diagnosis
families constitute an area of critical conditions that may influence
of ASD may reflect diagnostic
need for resources, research, and outcome and affect daily function.
substitution, the recognition of ASD in
professional education. The primary care provider can help
children previously primarily
minimize disparities in age of
diagnosed with intellectual disability
In the 12 years since the American diagnosis of African American and
or a co-occurring genetic syndrome.10
Academy of Pediatrics (AAP) Hispanic children and be alert to the
A true increase in the prevalence of
published the clinical report potential for gender bias in symptom
ASD associated with other biological
“Identification and Evaluation of recognition.7 This updated document
risk factors is also possible.
Children With Autism Spectrum aims to provide primary care
Disorders”5 and its companion, providers with a summary of current Prevalence rates in US populations
“Management of Children With information in a single report that are similar to those of other
Autism Spectrum Disorders,”6 will help guide them in providing industrialized countries,11 and lower
reported prevalence rates of ASD in a medical home for the patient rates are reported in resource-limited
children have increased, with ASD. countries, where epidemiological data
understanding of potential risk are more difficult to collect.12 Data on
factors has expanded, awareness of national samples suggest that the
co-occurring medical conditions and SECTION 1: PREVALENCE prevalence of ASD is stabilizing.2,13
genetic contribution to etiology has Incidence is the onset of new Ongoing epidemiological studies help
improved, and the body of research diagnoses over time in a selected to understand changes in the
supporting evidence-based cohort. Without consistent reported prevalence over time.
interventions has grown substantially. longitudinal data in a specified Epidemiological data help to predict
This updated clinical report builds on cohort, incidence cannot be the need for services and identify
previous reports and guidance for determined. Because of the potential risk factors. Surveillance
care of children and youth with ASD. heterogeneity of symptoms and methods include regional, state,
It also reflects changes in diagnostic severity in ASD, it may be diagnosed and/or national registry systems;

2 FROM THE AMERICAN ACADEMY OF PEDIATRICS
records- or services-based analyses; as having ASD before 3 years of age. developmental and behavioral
surveys; and other methods, including Diagnosis later than 6 years of age disorders and symptoms. In the years
population-based case findings. was reported in one-third to half of since the 2007 AAP clinical reports on
children. Later age at diagnosis was ASD, both professional education and
In 2000, the US Centers for Disease associated with reported mild public awareness have promoted
Control and Prevention (CDC) presentation.16 recognition of symptoms that might
established the Autism and lead to early identification of ASD,
Developmental Disabilities CDC surveillance data published in
use of standardized screening
Monitoring (ADDM) Network as 2014 revealed that white, non-
approaches, and management of
a population-based public health Hispanic children were approximately
associated medical and behavioral
surveillance system to estimate the 20% more likely to be identified with
features of ASD from infancy through
prevalence of ASD in children 8 years ASD before the case review than were
adolescence.
of age. ADDM reports published in non-Hispanic African American
2014 and 2016 revealed comparable children and were about 50% more
prevalence rates (approximately 1 in likely to be identified with ASD than Core Symptoms
68),14,15 but the report published in were Hispanic children.14 Recent
prevalence data reveal increasing Although symptoms of ASD are
20182 revealed a slightly increased
rates of ASD in Hispanic and African neurologically based, they manifest as
rate (1 in 59). Additional data over
American children. This may reflect behavioral characteristics that
time will help determine if rates have
more widespread awareness of the present differently depending on age,
stabilized. The data also revealed
symptoms among parents, schools, language level, and cognitive abilities.
some variation in prevalence rates
and health care providers and Core symptoms cluster in 2 domains
across the participating states, with
improved rates of screening in health (social communication/interaction
the highest rates in the locations
supervision care.2 Studies examining and restricted, repetitive patterns of
where both educational and health
the effects of race and ethnicity on behavior), as described in the DSM-
records were available for chart
age at diagnosis are conflicting,7 but 5.1 Atypical development in several
abstraction and standardized
earlier diagnosis of ASD is associated functional areas contribute to
application of diagnostic criteria.
Regional variation in prevalence may with higher socioeconomic status and symptoms of ASD. Abnormalities in
also reflect availability of services, access to services. African American understanding the intent of others,
local provider practices for ASD and Hispanic children diagnosed with diminished interactive eye contact,
screening, educational policies, school ASD by age 4 years were more likely and atypical use and understanding
and/or community resources, and to have coexisting intellectual of gesture presage atypical
insurance mandates, among other disability than were white, non- development of social communication
factors. The CDC also published data Hispanic children, suggesting that and pretend play as well as interest in
on the prevalence of ASD in children some African American and Hispanic other children. Symptoms of ASD are
who were 4 years of age in 2010. A children with ASD and average to further shaped by deficits in imitation
lower prevalence rate for diagnosis above-average intelligence may not and of processing information across
(1.34%) was reported in these have been identified.17 sensory modalities, such as vision
children (approximately 30% less (gesture) and hearing (language).
than that of children 8 years of age). Repetitive behaviors and
The lower identified prevalence and SECTION 2: CLINICAL SYMPTOMS perseveration may be primary
higher proportional rate of children Despite advances in understanding compulsions but may also be related
4 years of age with ASD and the neurobiology and genetics of ASD, to atypical processing of sensory
intellectual disabilities may be the diagnosis of ASD continues to be information or may reflect a desire to
attributable, in part, to later diagnosis based on identifying and reporting instill predictability when an
of children with ASD and average- behaviorally defined clinical individual does not understand the
range cognitive abilities.16 The symptoms. The challenges in intent of others. The CDC “Learn the
National Survey of Children’s Health determining accurate prevalence Signs. Act Early” Web site provides
(2011–2012) and the National Survey rates, in part, relate to the need for free resources to help families
of Children with Special Health Care consistency in clinical diagnosis of recognize developmental concerns,
Needs (2009–2010) were analyzed a very heterogeneous disorder. In including autism (https://www.cdc.
for the age the parents reported 2013, the DSM-5 consolidated the gov/ncbddd/actearly/), and Autism
diagnosis as well as for parent- diagnosis of ASD into a single Navigator (www.autismnavigator.
reported subjective severity. The category and emphasized the com) has a video glossary of early
minority of children were identified importance of identifying coexisting symptoms in toddlers.

PEDIATRICS Volume 145, number 1, January 2020 3
Approximately one-quarter of paired with inconsistency in their agreement of surveillance data by
children with ASD will be reported to application across research sites using DSM-IV-TR and DSM-5 criteria.
have a regression in language or supports the decision to consolidate
The DSM-5 criteria have been shown
social skills, most typically between the subgroups into 1 diagnostic
to appropriately identify younger
18 and 24 months of age.18,19 The category, ASD, in the DSM-5. The
children and those with mild
reason for this loss of previously DSM-IV divided the symptoms of ASD
symptoms.25,27 These children with
acquired milestones is not yet known. into 3 areas: qualitative impairment
milder cognitive and adaptive
Although medical evaluation of loss of of social reciprocity, qualitative
symptoms may be the ones most
milestones is indicated, a history of impairment of communication, and
likely to have significant change with
regression in language and social restricted and repetitive behaviors. In
early intervention services.
interaction in children with ASD the DSM-5, core symptoms were
within the expected age range is not divided into 2 domains (social The DSM-5 also introduced an
likely to be attributable to seizures or communication and social interaction approach to severity rating, which is
neurodegenerative disorders. Note and restrictive, repetitive patterns of summarized in Table 2. Severity
that the processes underlying behaviors).23 To fulfill diagnostic rating reflects the impairment of the
regression are not yet well criteria for ASD by using the DSM-5, ASD symptoms and the resultant
understood. Current theories include all 3 symptoms of social affective service needs of the individual.
synaptic “over pruning” in response difference need to be present in Severity rating is not a quantifiable
to genetic factors.20 addition to 2 of 4 symptoms related score that can be used to monitor
to restrictive and repetitive progress at this time; in clinical use, it
Diagnostic Criteria: DSM-5 behaviors. Examples in Table 1 are often reflects the impact of cognitive
The DSM has been central in illustrative but not exhaustive. The limitations.28 Measures have been
establishing criteria for diagnosing recognition of symptoms of ASD published that attempt to capture
mental and behavioral disorders. The related to sensory processing led to severity of core symptoms29,30 and
diagnosis of infantile autism was the inclusion of sensory symptoms, allow for measurement of
introduced in the Diagnostic and such as hyper- or hyporeactivity to improvement with intervention.31 To
Statistical Manual of Mental Disorders, sensory input or unusual interests in date, no single measure adequately
Third Edition nearly 30 years after sensory aspects of the environment. reflects the combination of medical,
the first edition of the DSM was Examples include apparent behavioral, and educational severity
published in 1952. The initial indifference to pain or temperature; in a fashion that will help clinicians
descriptions were narrow and sensitivity to sound, taste, or textures; and families determine progress with
referred to individuals with profound and intense visual interest in objects intervention across multiple
impairment. Publication of the DSM- or movement. The DSM-5 notes that functional domains. Coexisting
IV in 1994 expanded the diagnosis to a diagnosis may be made at older medical disorders also affect the
a spectrum of symptoms called ages, when the demands of the social perception of severity and the
pervasive developmental disorders or school environment may result in prognosis for children with
(PDDs), which included the diagnoses functional impairment. a diagnosis of ASD. The DSM-5
of autistic disorder, Asperger includes course specifiers that help
disorder, pervasive developmental Almost all individuals with describe the variation in symptoms of
disorder not otherwise specified a diagnosis of autistic disorder or individuals with ASD. Course
(PDD-NOS), childhood disintegrative Asperger syndrome by using DSM-IV specifiers include the presence or
disorder, and Rett disorder. The PDDs criteria would be diagnosed with ASD absence of intellectual impairment,
included individuals with lower- and by using DSM-5 criteria.24 To language impairment, catatonia,
higher-functioning cognitive skills. determine if the same patients would medical conditions, and known
PDD-NOS was a diagnostic category be identified by the DSM-IV and DSM- genetic or environmental etiologic
requiring some, but not all, of the core 5 criteria, the CDC ADDM Network factors. Patients with Rett syndrome
symptoms necessary for other looked at its chart abstraction data on are no longer automatically
diagnoses in this category. 8-year-old children.25 This analysis considered to have a diagnosis of ASD
Subsequent research has revealed that more than 80% of according the DSM-5, although
demonstrated that the subgroupings children diagnosed with PDD-NOS individuals with this neurogenetic
within PDD were not reproducible would also be diagnosed with ASD.25 disorder may also meet diagnostic
across research sites by using the It is possible that the narrative in the criteria for ASD. Specific genetic
same diagnostic data21,22 and were charts that were abstracted was causes of ASD should be recorded as
not stable over time. The overlap influenced by knowledge of the DSM- specifiers for individuals with ASD
between DSM-IV–defined subgroups IV criteria.26 There is a high level of when identified. The DSM-5 promotes

TABLE 1 DSM-5 Criteria for Autism Spectrum Disorder
Domains Criteria: Deficits Examples
A. Persistent deficits in social communication and social 1. Social-emotional reciprocity Abnormal social approach and failure of normal back-
interaction across multiple contexts, as manifested and-forth conversation; reduced sharing of interests,
by the following, currently or by history; must have emotions, or affect; failure to initiate or respond to
all 3 symptoms in this domain social interactions
2. Nonverbal communicative behaviors Poorly integrated verbal and nonverbal communication;
used for social interaction abnormalities in eye contact and body language or
deficits in understanding and use of gestures; total
lack of facial expressions and nonverbal
communication
3. Developing, maintaining, and Difficulties adjusting behavior to suit various social
understanding relationships contexts; difficulties in sharing imaginative play or in
making friends; absence of interest in peers
B. Restricted, repetitive patterns of behavior, interests, 1. Stereotyped or repetitive motor Simple motor stereotypies, lining up toys or flipping
or activities, as manifested by at least 2 of the movements, use of objects, or speech objects, echolalia, idiosyncratic phrases
following, currently or by history; must have 2 of the
4 symptoms
2. Insistence on sameness, inflexible Extreme distress at small changes, difficulties with
adherence to routines, or ritualized transitions, rigid thinking patterns, greeting rituals,
patterns or verbal nonverbal behavior need to take same route or eat food every day
3. Highly restricted, fixated interests that Strong attachment to or preoccupation with unusual
are abnormal in intensity or focus objects, excessively circumscribed or perseverative
interest
4. Hyper- or hyporeactivity to sensory Apparent indifference to pain/temperature, adverse
input or unusual interests in sensory response to specific sounds or textures, excessive
aspects of the environment smelling or touching of objects, visual fascination with
lights or movement
Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities or may be masked by learned strategies
in later life). Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning. These disturbances are not better explained by
intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and ASD frequently co-occur; to make comorbid diagnoses of ASD and
intellectual disability, social communication should be below that expected for the general developmental level. Specify whether: with or without accompanying intellectual impairment,
language impairment or associated with a known medical or genetic condition or environmental factor. Add code 293.89 if catatonia is also present. Reprinted with permission from the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (copyright 2013). American Psychiatric Association. All Rights Reserved.
notation of all coexisting diagnoses as and social communication disorder continues to include the subtypes of
specifiers. are similar and different in terms of diagnoses as defined by the DSM-IV.33
etiology, prognosis, and treatment. The DSM-5 provides the clinician with
Social pragmatic communication Evaluation of pragmatic (social) criteria and definitions for diagnosis
disorder is a new diagnosis described language use by a speech-language of ASD and should guide the clinician
within the DSM-5 that describes pathologist provides additional in the diagnosis and management
individuals who exhibit functionally information to consider this of ASD.
impairing symptoms in social diagnosis.32 The characteristics of
language use but do not have habitual social pragmatic communication Co-occurring Symptoms and
or repetitive behaviors.1 Individuals disorder and how best to address Conditions
who are affected must have deficits in symptoms require additional study. Co-occurring conditions are common
using language for social purposes, in children with ASD and may have
impaired ability to match their Although the DSM-5 provides the great effects on child and family
communication style with the context criteria and definitions to accurately functioning and clinical management
for communication, difficulty assign mental health and behavioral (see also Section 5: Interventions).
following the conventional rules for diagnoses, the International Examples include medical conditions
conversation, and difficulty with Classification of Diseases, 10th such as sleep disorders and seizures;
idioms and unstated meanings in Revision, Clinical Modification is the other developmental or behavioral
language (Table 3). As with ASD, the standardized code set used for diagnoses, such as attention-deficit/
symptoms cannot be better explained payment as well as for statistical hyperactivity disorder (ADHD),
by another DSM-5 diagnosis. tracking through electronic medical anxiety, and mood disorders; and
Research and experience with DSM-5 records. The International behavioral disorders, such as food
diagnoses over time will give Classification of Diseases, 10th refusal, self-injury, and aggression.34
clinicians a better sense of how ASD Revision, Clinical Modification Approximately 30% of children with

TABLE 2 ASD Symptoms by Level of Severity
Severity Level Social Affective Restricted and Repetitive Behaviors
Level 1. “Requiring Without supports in place, deficits in social communication cause Inflexibility of behavior causes significant interference with
support” noticeable impairments. Difficulty initiating social interactions, functioning in one or more contexts. Difficulty switching
and clear examples of atypical or unsuccessful response to between activities. Problems of organization and planning
social overtures of others. May appear to have decreased hamper independence.
interest in social interactions.
Level 2. “Requiring Marked deficits in verbal and nonverbal social communication Inflexibility of behavior, difficulty coping with change, or other
substantial support” skills. Social impairments apparent even with supports in restricted and repetitive behaviors appear frequently enough to
place. Limited initiation of social interactions and reduced or be obvious to the casual observer and interfere with
abnormal responses to social overtures from others. functioning in a variety of contexts.
Distress and/or difficulty changing focus or action.
Level 3. “Requiring very Severe deficits in verbal and nonverbal social communication Inflexibility of behavior, extreme difficulty coping with change, or
substantial support” skills cause severe impairments in functioning, very limited other restricted and repetitive behaviors markedly interfere
initiation of social interactions, and minimal response to social with functioning in all spheres. Great distress at or difficulty
overtures from others. with changing focus or action.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (copyright 2013). American Psychiatric Association. All Rights Reserved.
a diagnosis of ASD will also have 3 years of age, especially if they have Approximately 9% of children who
intellectual disability,2 and 30% are average or above-average cognitive are diagnosed with ASD in early
minimally verbal.35 Increasingly, abilities.38 Across early childhood childhood may not meet diagnostic
researchers and clinicians recognize development, communication skills criteria for ASD by young adulthood.
how co-occurring disorders help and social affective symptoms may Youth who no longer meet criteria for
identify phenotypic differences improve, whereas repetitive ASD are more likely to have a history
within populations affected by ASD, behaviors may change, possibly of higher cognitive skills at 2 years of
which can influence prognosis and reflecting maturation and/or age, to have participated in earlier
choice of interventions. intervention.39 In general, young intervention services, and to have
children with ASD with language
Prognosis demonstrated a decrease in their
impairment appear to have more
repetitive behaviors over time.41 A
The prognosis and trajectory of social difficulty than do children with
change in clinical diagnosis (eg, to
development for a young child ASD without language impairment.
ADHD or obsessive-compulsive
diagnosed with ASD typically cannot Children with ASD and intellectual
be predicted at the time of diagnosis. disability have the most difficulty disorder [OCD]) is more likely in
However, most children ($80%) who developing social competence.40 The children who were diagnosed with
are diagnosed with ASD after prognosis for children with ASD in ASD before 30 months of age or had
a comprehensive evaluation at less phenotypic and demographic a diagnosis of PDD-NOS per the DSM-
than 3 years have retained their subgroups (eg, girls, racial and IV.42,43 Severity scores are most likely
diagnosis.36,37 It may be more ethnic subgroups, children with to improve in youth who have had the
difficult to recognize mild symptoms macrocephaly) needs additional greatest increase in tested verbal
of ASD in children younger than study. IQ.44 Executive function difficulties
TABLE 3 DSM-5 Social (Pragmatic) Communication Disorder (DSM-5 315.39)

A. Persistent difficulties in the social use of verbal and nonverbal communication as manifested by all of the following:
1. Deficits in using communication for social purposes, such as greeting and sharing information, in a manner that is appropriate for the social context.
2. Impairment of the ability to change communication to match context or the needs of the listener, such as speaking differently in a classroom than on the
playground, talking differently to a child than to an adult, and avoiding use of overly formal language.
3. Difficulties following rules for conversation and storytelling, such as taking turns in conversation, rephrasing when misunderstood, and knowing how to
use verbal and nonverbal signals to regulate interaction.
4. Difficulties understanding what is not explicitly stated (eg, making inferences) and nonliteral or ambiguous meanings of language (eg, idioms, humor,
metaphors, multiple meanings that depend on the context for interpretation).
B. The deficits result in functional limitations in effective communication, social participation, social relationships, academic achievement, or occupational
performance, individually or in combination.
C. The onset of the symptoms is in the early developmental period (but deficits may not become fully manifest until social communication demands exceed
limited capacities).
D. The symptoms are not attributable to another medical or neurologic condition or to low abilities in the domains or word structure and grammar and are not
better explained by ASD, intellectual disability (intellectual developmental disorder), global developmental delay, or another mental disorder.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (copyright 2013). American Psychiatric Association. All Rights Reserved.

are associated with poorer adaptive TABLE 4 Red Flags: Early Symptoms of ASD
outcomes, independent of IQ.45 Symptom
Measured intelligence (eg, IQ) and By 12 months • Does not respond to name
language ability in childhood tend to By 14 months • Does not point at objects to show interest
predict outcome in adulthood.46 By 18 months • Does not pretend play
However, reported quality of life in General • Avoids eye contact and may want to be alone
high-functioning adults with ASD was • Has trouble understanding other people’s feelings or talking about their own feelings
• Has delayed speech and language skills
associated more with the presence of • Repeats words or phrases over and over (echolalia)
family and community supports than • Gives unrelated answers to questions
their symptoms related to ASD.47 • Gets upset by minor changes
• Has obsessive interests
• Makes repetitive movements like flapping hands, rocking, or spinning in circles
SECTION 3: SCREENING AND DIAGNOSIS • Has unusual reactions to the way things sound, smell, taste, look, or feel
Information from this table is adapted from http://www.cdc.gov/ncbddd/autism/signs.html.
The AAP recommends screening all
children for symptoms of ASD
through a combination of developed by the CDC may help primary pediatric care have increased
developmental surveillance at all educate families about developmental steadily. In the 2015 AAP survey of
visits and standardized autism- and behavioral milestones (https:// screening practices, almost three-
specific screening tests at 18 and www.cdc.gov/ncbddd/actearly/ quarters of pediatricians who
24 months of age in their primary index.html). Developmental responded reported routine ASD
care visits5 because children with surveillance alone is not sufficient to screening.54 Pediatricians
ASD can be identified as toddlers, and identify children who need further increasingly report including office
early intervention can and does evaluation because children with ASD staff for efficient workflow, including
influence outcomes.48 This autism- may not demonstrate characteristic administration and scoring of
specific screening complements the symptoms in brief office visits,50 and screening tests. Although time and
recommended general developmental caregivers may not volunteer social remuneration remain as concerns,
screening at 9, 18, and 30 months of and emotional concerns unless fewer pediatricians rate these as
age.9 Efficient screening of all specifically asked. Use of barriers. Referral for and tracking of
children would be aided by inclusion a standardized screening tool for ASD evaluation and services remain
of valid screening tools in the can help families identify potential a challenge associated with lack of
electronic health record with symptoms. In a large study evaluating office-based systems for making
appropriate compensation for the universal screening with the Modified referrals and after screen-positive
staff and professional time necessary Checklist for Autism in Toddlers outcomes.43
to complete the administration, (M-CHAT), researchers asked
scoring, and counseling related to The authors of the 2019 AAP
physicians to note whether they were
screening.49 developmental surveillance and
concerned about ASD. Sensitivity of
screening clinical report discuss
physician clinical concern was low
Screening tools are designed to help strategies for billing for screening
(0.244; 30 of 123 cases; 95%
caregivers identify and report and counseling in primary care. 49
confidence interval 0.17–0.32). The
symptoms observed in children at The following sections describe
sensitivity of the M-CHAT when used
high risk for ASD. The screens are tools commonly used to screen and
as directed in this low-risk population
based on early manifestations of diagnose ASD and emphasize the
was 0.91.51 Accurate early
symptoms of core deficits related to importance of ongoing
identification has been a goal of the
social communication. Some of these surveillance, especially in children
AAP since the publication of the 2
early symptoms that may alert the at high risk.
previous autism clinical reports in
provider to the risk for ASD have
2007, with focused continuing
been called “red flags” (Table 4). Screening
medical education and a tool kit (AAP
Developmental surveillance for ASD Autism Toolkit: https://toolkits. Results of a screening test are not
includes asking caregivers about solutions.aap.org/toolkits.aspx). The diagnostic; they help the primary care
concerns they have about their child’s goal of universal screening, including provider identify children who are at
development or behavior, informal screening for ASD, has been risk for a diagnosis of ASD and
observation, and monitoring of supported by public health agencies52 require additional evaluation. General
symptoms in the context of routine and family support organizations.53 developmental screening tools used
health supervision. The “Learn the Rates of screening for both for screening at ages 9, 18, and
Signs. Act Early” parent resources developmental delays and ASD in 30 months identify language,

cognitive, and motor delays but may Screening by Age Group ASD. Pediatricians can help families
not be sensitive to social symptoms Children Younger Than Age 18 Months with management of these symptoms.
associated with identification of
Earlier diagnosis of ASD may lead to
ASD.43,55 This limitation associated Children Ages 18 to 30 Months
earlier treatment. The M-CHAT is the
with general developmental
most studied and widely used tool The most commonly used
screening is why ASD-specific tools56
for screening toddlers for ASD. questionnaire-based screening tool is
are needed to capture differences in
Additional tools are under the M-CHAT. It has been further
social interaction, play, and
investigation and are listed in Table 6 validated, and the scoring has been
repetitive behaviors. See the AAP modified for ease of administration in
as promising autism screening tests.
clinical report “Promoting Optimal primary care settings for children
Language delay can be identified by
Development: Identifying Infants ages 16 to 30 months.51 The Modified
using the Infant and Toddler
and Young Children With Checklist for Autism in Toddlers,
Checklist (parent questionnaire) in
Developmental Disorders Through Revised with Follow-Up (Questions)
low-risk infants and toddlers between
Developmental Surveillance and (M-CHAT-R/F) eliminates 3 questions
12 and 18 months of age.43,59 This
Screening,”49 Table 1 (developmental from the previous version. Children
questionnaire might be useful in
screening tests; a description of who score $8 are at high risk for ASD
identifying infant siblings of children
general developmental and or another developmental disorder
with ASD who are at increased risk
behavioral screening tests), and and should be referred immediately
for ASD. Additional research may
Table 5 in this report for resources for diagnostic assessment. For
allow for screening of toddlers as
and guidance on developmental children with scores of 3 to 7, publicly
young as 12 months by using parent-
screening. available scripted follow-up interview
administered questionnaires such the
Communication and Symbolic questions are required for the items
Parent-completed questionnaires
Behavior Scales Development Profile scored as positive. Children who
are the most common screening
and the Infant and Toddler continue to have 3 to 7 items positive
tests used in primary care.
Checklist.58 for ASD diagnosis after clarifying
Commonly used autism-specific
follow-up questions have a 47% risk
screening tools that are based on Primary care providers are tasked
of having ASD diagnosed and a 95%
questionnaires and observation are with identifying all children who
chance of being identified with some
summarized in Table 6. Many would benefit from early
other developmental delay that would
clinician-administered screening intervention, not just children at risk
benefit from intervention. Children
tests require specific training (eg, for ASD (see the AAP clinical report
screened with the M-CHAT-R/F are
the Screening Tool for Autism in “Promoting Optimal Development:
identified with ASD at younger ages
Toddlers and Young Children Identifying Infants and Young
than predicted by national
[STAT]).5,57 A clinician- Children With Developmental
statistics.49 Children who do not pass
administered test like the STAT Disorders Through Developmental
ASD screening tests or who score as
increases the likelihood of an ASD Surveillance and Screening”49 for
at risk for a diagnosis should be
diagnosis on further testing and further information). It is important
referred for both diagnostic
may be used to support to identify all clinically significant
assessment and intervention services.
a preliminary diagnosis of ASD to delays in children with referral for
A definitive diagnosis is not necessary
obtain services.58 Identification of appropriate diagnostic evaluation and
to institute services for documented
infants and toddlers at risk for ASD intervention. Problems with sleep,
delays that would be served through
based on neurophysiologic makers eating, constipation, and state
early intervention or school services.
or other biomarkers is discussed in regulation are common in the general
Although the M-CHAT-R/F appears to
the subsection The Biology of ASD in population but may be particularly
be useful for general screening of
Section 4: Etiologic Evaluation. challenging in young children with
diverse populations,60 decreasing the
disparity in early diagnosis will
TABLE 5 Resources and Guidance for Developmental Screening require adapting and validating
measures and addressing cultural and
• AAP Bright Futures: Guidelines for the Health Supervision of Infants, Children, and Adolescents
• AAP early childhood screening linguistic barriers to screening.61
• AAP clinical report: “Promoting Optimal Development: Identifying Infants and Young Children With
Developmental Disorders Through Developmental Surveillance and Screening”49
Measures under development may
• Additional guidance for developmental and behavioral screening can be found in “Birth to 5: Watch provide rapid screening while
Me Thrive!” which contains helpful information for the primary care provider about how to present addressing clinician concerns for
the results of developmental screening (available at: https://www.acf.hhs.gov/sites/default/files/ecd/ compatibility with an electronic
pcp_screening_guide_march2014.pdf). record system and open access.62

TABLE 6 Commonly Used ASD Screening Tests
Autism Screening Description Age Range Average No. Administration Forms Available Psychometric Scoring Method Cultural Source Key References
Tests Items Time EHR compatible Properties Considerations
M-CHAT-R/F Parent-completed 16–30 mo 20 5–10 min Yes Standardization Risk categorization Available in http://mchatscreen. Ref 51
questionnaire sample included for questionnaire multiple com/
designed to 16 071 children (pass/need languages;
identify children screened; 115 interview/ fail); see test
at risk for had positive after interview information
autism from the screen results, (pass/fail) for details
general 348 needed
population; evaluation, 221
follow-up were evaluated,
clinician- and 105
administered diagnosed with
PEDIATRICS Volume 145, number 1, January 2020

questions and an ASD; validated
repeat by using the ADI-
questionnaire R, ADOS-G, CARS,
required for and DSM-IV-TR;
specificity sensitivity: 0.91;
specificity: 0.95
for low-risk 18-
and 24-mo-old
children with
follow-up
questionnaire
and interview;
45% of children
with a score $3
on the initial
screen and $2
on follow-up had
ASD; 95% had
clinically
significant
developmental
delay

SCQ Parent-completed 41 y 40 5–10 min No Validated by using Risk categorization Available in Western Refs 77 and 572
questionnaire; the ADI-R and (pass/fail) multiple Psychological
designed to DSM-IV on 200 languages; Corporation: www.
identify children subjects (160 see test wpspublish.com
at risk for ASD with pervasive information
from the general developmental for details.
population; disorder, 40
based on items without pervasive
in the ADI-R developmental
disorder); for use
in children with
mental age of at
9
10
TABLE 6 Continued
least 2 y and
chronologic age
41 y; available in
2 forms: lifetime
and current.
overall test:
sensitivity: 0.85
(moderate),
specificity: 0.75
(moderate);
sensitivity can be
improved with
lowering cutoff
for children
younger than 5 y
and 5–7 y,
specificity poor
for younger
children
STAT Clinician-directed, 24–35 mo; 12 20–30 min No Validated by 12 activities to English http://stat. Refs 573 and
interactive, and ,24 mo comparison with observe early vueinnovations. 574
observation (exploratory) ADOS-G results in social- com/
measure; 52 children 24–35 communicative
requires training mo (26 with behavior; risk
of clinician for autism, 26 with categorization
standardized developmental (high risk/low
administration; delay); sensitivity: risk)
not for 0.83, specificity:
population 0.86, PPV: 0.77,
screening NPV: 0.90, for
,24 mo:
sensitivity: 0.95,
specificity: 0.73,

PPV: 0.56, NPV:
0.97; screening
properties
improved for
children .14 mo
Promising autism
screening tests
The Infant/Toddler Parent 6–24 mo 24 15 min No PPV DD: 0.43 (6–8 Identifies language Available in Paul H. Brookes Ref 59
Checklist questionnaire: mo); PPV DD: 0.79 delays (alone/ multiple Publishing Co Inc:
(Communication screens for (21–24 mo) with ASD); risk languages; 800-638-3775 or
and Symbolic language delay for ASD; risk see test www.
Behavior Scales status for social,
FROM THE AMERICAN ACADEMY OF PEDIATRICS

TABLE 6 Continued
Developmental speech, symbolic information brookespublishing.
Profile) composites, and for details com
total score
Early Parent 12–36 mo 47 10–15 min No Sensitivity: Investigation English https:// Not in peer-
Screening for questionnaire: 0.85–0.91; ongoing of firstwordsproject. reviewed
Autism and research edition, specificity: subset (24 com/screen- literature
Communication 47 items 0.82–0.84; PPV: items) my-child/
Disorders 0.55–0.81; NPV:
0.88–0.98
First-Year Inventory Parent 12 mo 63 10 min No Sensitivity, Scores at risk; English https://www.med.unc. Ref 575
questionnaire; specificity, PPV promising in edu/ahs/pearls/
PEDIATRICS Volume 145, number 1, January 2020

promising in not reported high-risk (infant research/first-
high-risk sibling) cohort year-inventory-fyi-
population to (Rowberry development/
identify risk in et al575)
12-mo-old
infants
Parent’s Parent 16–35 mo 7 ∼5 min Available Sensitivity: 3 of 7 symptoms in Available in Free download from Publications
Observations of questionnaire through 83%–93%, at-risk range multiple www.theswyc.org and User’s
Social used to assess patient tools, average 88.5%; languages; Manual
Interactions autism risk; ASD epic, and specificity: see test available at
screening CHADIS; 42%–75%, information www.
included on 18-, available for average 56.9% for details theswyc.org;
24-, and 30-mo free Refs 576 and
The Survey of download as 577
Well-Being of pdfs from
Young Children: www.
forms theswyc.org
Rapid Interactive Clinician 12–36 mo 9 20–30 min No Cutoff .15; 9 interactive English https://umassmed. Ref 578
Screening Test observation: interactive sensitivity: 1; activities; total edu/AutismRITA-T/
for Autism in administered by items specificity: 0.84; score summed, about-the-test/
Toddlers 13 trained examiner PPV: 0.88; NPV: cutoff score of 15
0.94; needs (for that sample)

further study in
larger samples
The AAP does not approve/endorse any specific tool for screening purposes. This table is not exhaustive, and other tests may be available. ADOS-G, Autism Diagnostic Observation Schedule – Generic; CARS, Childhood Autism Rating Scale; CHADIS,
Comprehensive Health and Decision Information System; EHR, electronic health record; ICD-10, International Classification of Diseases, 10th revision; IMFAR, International Meeting for Autism Research; NPV, negative predictive value; PPV, positive
predictive value.
11
Further adaptations of the AAP continues to recommend Barriers to Identifying Risk for ASD
Communication Symbolic Behavior screening using the most valid of Children with milder symptoms
Scale for use in screening for current measures at 18 and and/or average or above-average
language delays in addition to ASD 24 months of age. Pediatricians intelligence may not be identified
have the potential to identify children cannot assume that early intervention with symptoms until school age,
at risk for both disorders (functional systems will screen participants when differences in social language
communication; ages 6–24 being served for language or global or personal rigidities affect function.
months).49,59 Use of this or other delays for ASD at the recommended Some children who are later
screening tools may be coupled with ages. Universal screening is diagnosed with ASD are initially
the online support of a video glossary recommended because symptoms of believed to have precocious language,
of symptoms of ASD, such as that in ASD can be identified in early reading, or math skills, and it is not
the Autism Navigator (http://www. childhood, and a diagnosis of ASD by until the social demands of school
autismnavigator.com/). These and skilled professionals is accurate in that the social language symptoms
other online approaches to support children as young as 18 months of become problematic. It has also been
screening strategies may be age.65 Diagnostic stability is high for suggested that girls may have lesser
integrated into efficient patterns of children who are diagnosed with ASD intensity of symptoms and fewer
practice. Results of screening at 18 to 36 months of age.43 Early externalizing behaviors. These
conducted online, in community screening does not identify many differences may, in part, result in
settings, and in preschools should be children with milder symptoms and underdiagnosis in girls.70 Specific
communicated to the primary care typical cognitive ability as at risk for coexisting conditions may prevent
provider to ensure appropriate ASD; therefore, ongoing surveillance clinicians from recognizing symptoms
evaluation of etiology, co-occurring remains necessary.16 Participation in of ASD in early childhood. For
conditions, referral for diagnosis, and early intervention in general is example, 1 study revealed that
follow-up to ensure that intervention greatest among children who had children who were initially identified
is accessed.49 screening and surveillance.66 with ADHD in primary care were
Children Older Than 30 Months diagnosed with ASD 3 years later
A systematic review by the US
compared with children who did not
Preventive Services Task Force At present, for children older than have earlier symptoms of ADHD.69
(USPSTF) concluded that the 30 months, there are no validated Recognition and referral for older
literature on existing screening tools screening tools available for use in children with social-skill deficits
did not demonstrate sufficient pediatric practice, nor are there would be facilitated by the
specificity to justify universal current recommendations by the AAP development of accurate and brief
screening.63 The USPSTF noted that for universal screening for ASD in screening tests for use in primary
no study has directly examined that age group. The Social care and school settings.
whether children with ASD detected Communication Questionnaire (SCQ)
by early screening have better (see Table 6) has been studied in Population surveillance data reveal
outcomes than those detected by different populations (eg, clinical later age at diagnosis for African
other means. However, such a study sample, population reference sample, American and Hispanic children,
would require random assignment of community sample, and convenience suggesting that there are barriers to
large representative samples from sample), with best results in screening and surveillance and
across the country to either population samples67 when using the referral for diagnosis in groups with
a screening or nonscreening lifetime version, and appears to have other unmet health needs.2 Race,
condition, with follow-up of long- reasonable psychometric properties. ethnicity, and socioeconomic status
term outcomes and societal costs. However, questionnaires like the SCQ did not affect the accuracy of routine
Given that early treatment of children may identify symptoms that overlap screening tests for ASD in low-risk
younger than 36 months has been with other conditions, such as ADHD, toddlers, suggesting that screening
shown to result in positive that affect function at school age.68,69 with appropriate supports for follow-
outcomes,43,64 such a study would be Further validation of population- up care can lower the age at diagnosis
challenging to support. The USPSTF based screening tools for children in diverse populations.60 Language
concluded that further research is older than 30 months is needed barriers, inaccurate translations, and
indicated to evaluate the appropriate before recommendations for low parental literacy may
ages and populations of children who universal screening of school-aged compromise use of parent-completed
should be screened for ASD and that children can be made. At this time, questionnaires.71 Limited
more accurate and culturally sensitive ongoing surveillance in the context of understanding of cultural differences
measures should be developed. The primary care is recommended. experienced by the patient’s family

and lack of trust in the health care function. Formal assessment of Elevated scores may be seen with
provider may further limit language, cognitive, and adaptive greater severity of symptoms of
identification and reporting of abilities and sensory status is an ASD as well as with intellectual
symptoms of autism.72 Screening important component of the disability, communication
tools need to be developed for diagnostic process. difficulties, and behavioral
populations of individuals whose challenges.
Short clinical visits may not allow
primary language is not English and
even a skilled clinician the Structured observation of symptoms
who are also sensitive to cultural
opportunity to accurately recognize of ASD during clinical evaluation is
barriers that may limit reporting of
symptoms of ASD.50 An accurate
symptoms of ASD.73 helpful to inform the diagnostic
history needs to reflect a longitudinal
application of the DSM-5 criteria.
experience with the individual and
Diagnostic Evaluation Validated observation tools used to
reflect the effects of symptoms on the
provide structured data to confirm
Once a child is determined to be at patient’s ability to function in family,
the diagnosis include the Autism
risk for a diagnosis of ASD, either by peer, and school settings. This history
Diagnostic Observation Schedule,
screening or surveillance, a timely is obtained by interview with the
Second Edition (ADOS-2) and the
referral for clinical diagnostic patient and caregivers, reports of
Childhood Autism Rating Scale,
evaluation and early intervention or behavior in other environments (such
Second Edition (CARS-2).86 No single
school services, depending on his or as school), and descriptions of
observation tool is appropriate for all
her age, is indicated.74 Children with behavior during formal testing. The
clinical settings. The observation tool
developmental delay with or without history of symptoms of ASD can be
is meant to support application of the
an ASD diagnosis should be referred supported by questionnaires such as
DSM-5 criteria informed by history
to early intervention or school the SCQ77 or Social Responsiveness
and other data.
services, in which cognitive and Scale (SRS).78 None of these
language testing may be completed. questionnaires is sufficient alone to The ADOS-2 was developed to elicit
The primary care provider should make a diagnosis of ASD, but all atypical social language and
discuss with the family the provide a structured approach to behaviors. With the ADOS-2, modules
importance of both the assessment of elicit symptoms of ASD. Measures are specific for use across the age
developmental status and evaluation such as the Behavior Assessment span of toddlers to adults.87,88 The
for an ASD diagnosis and assist the System for Children,79 Diagnostic ADOS-2 requires intensive training to
family in navigating through the Interview for Social and accurately administer and score and
process, including connecting them Communication Disorders takes 30 to 45 minutes to administer.
with community resources. Families (DISCO),80,81 and the Child Behavior It is often a component of both
with low income or language barriers Checklist82 are used to assess research and clinical evaluations. The
may need additional attention to take children and youth for other information obtained from the ADOS-
the next steps. behavioral health conditions but may
2 is used by the clinician in
also identify behavioral profiles
Although most children will need to conjunction with the history of peer
consistent with ASD.
see a specialist, such as interactions, social relationships, and
a developmental-behavioral or In some clinical and research functional impairment from
neurodevelopmental pediatrician, settings, the behaviors associated symptoms to determine if the DSM-5
psychologist, neurologist, or with ASD are reported through the criteria are met. The CARS-2 is
psychiatrist, for a diagnostic Autism Diagnostic Inventory- another structured approach
evaluation, general pediatricians and Revised (ADI-R), a lengthy, a clinician might use to support
child psychologists comfortable with semistructured parent a clinical diagnosis of ASD.89 The
application of the DSM-5 criteria can interview.83,84 It supports clinician completes a 15-point scale
make an initial clinical diagnosis. a knowledgeable clinician in that is based on history and
Having a clinical diagnosis may applying diagnostic criteria of ASD. observation. The ADOS-2, CARS-2,
facilitate initiation of services. At this The SCQ was designed to elicit and SRS (Parent and Teacher) all rate
time, there are no laboratory tests similar information to the ADI-R in children similarly in approximately
that can be used to make a diagnosis an abbreviated questionnaire half of identified cases.90 The
of ASD, so careful review of the child’s format. The SRS is a 65-item integration of historical information
behavioral history and direct questionnaire that may be used to and objective observation by
observation of symptoms are measure autistic traits on a clinician trained to diagnose autism
necessary.75,76 To meet diagnostic a continuum as part of a more and related conditions to inform the
criteria, the symptoms must impair complete evaluation of ASD.78,85 DSM-5 diagnostic criteria is the

critical element to diagnostic and nonverbal communication for problems, or inattention. Appropriate
evaluation. social interaction. Formal assessment amplification should be offered, if
of communication by a speech or indicated. The clinical utility of
Evaluation of Co-occurring language pathologist at the time of auditory processing evaluations
Developmental Conditions diagnosis should include the available in current practice remain
Patients with ASD may have documentation of expressive and an area of study.100,101
intellectual disabilities, learning receptive language skills as well as
disabilities, ADHD, anxiety disorders, the pragmatic or conversational use Sensory Assessment: Vision
or speech and language disorders, of language.92 Visual function should be considered
among others. These conditions may in the initial evaluation of children
influence the presentation of the Adaptive Function Testing
who are visually inattentive, have
symptoms of ASD. These conditions A caregiver report and/or teacher stereotypical behaviors (such as eye
may influence the presentation of report of adaptive functioning poking or close visual scrutiny), or do
symptoms of ASD and may influence complements objective cognitive not make eye contact. Decreased
the social and functional impairment testing. Determining the extent that visual acuity may affect interactive
of the individual in different ways at ASD affects daily function is gaze and require accommodations in
different ages. Valid assessment of necessary to establish eligibility for the educational setting.102 Children
cognitive and language ability is an some publicly funded programs as with visual impairment may also
important component of the well as to identify and monitor demonstrate stereotyped motor
diagnostic evaluation. In the United developmental goals for treatment. behaviors.
States, early intervention services and Adaptive behaviors are typically
school systems will evaluate children delayed in people who have Sensory Assessment: Sensory
in these domains to assess intellectual disability with ASD but Processing
educational needs. In some areas, can be impaired in people with ASD The DSM-5 includes sensory
initial evaluations are performed in and an average-range IQ.93,94 symptoms in the diagnostic criteria
clinical settings and paid for by Commonly used adaptive measures for ASD. The DSM-5 does not include
insurance. include the Vineland Adaptive sensory processing disorder as
Behavior Scales and the Adaptive a discrete diagnosis. Commonly used
Cognitive Testing Behavior Assessment System.95 evaluation tools (such as the Short
A range of standardized measures are Sensory Profile and others) quantify
used to determine developmental Motor Assessment
parent perception of sensory
levels of younger children and IQ in Children with ASD are more likely to differences relative to smell, taste,
children older than 3 years. The have mild delays in gross motor skills vision, hearing, and touch.103,104 In
intelligence test selected by the and coordination compared with addition to capturing what is
psychologist will depend on the age children in the general population conventionally considered as
and language level of the child. and may meet DSM-5 criteria for a sensory disturbance, questionnaires
Administration of a valid cognitive developmental coordination disorder that are used to assess sensory
test is important in ascribing in addition to ASD.96 General symptoms also capture motor
symptoms to ASD as part of the initial screening tests or adaptive measures hyperactivity and hypoactivity as
diagnosis but also helps to establish may suggest motor delays that would sensory-seeking or sensory-avoiding
co-occurring diagnoses with ASD, benefit from formal evaluation by an behaviors. These latter symptoms
such as intellectual disability. There occupational or physical therapist. A may reflect co-occurring ADHD.
are valid tests that can be used in relationship of early motor delays and Sensory symptoms may be more
children who are nonverbal. Although subsequent language and adaptive evident at younger ages and may
the prevalence of a diagnosis of ASD development in children with ASD define subtypes of the disorder.105,106
is increased in children with an has been proposed.97,98
intellectual disability,91 other children
diagnosed with intellectual disability Sensory Assessment: Hearing SECTION 4: ETIOLOGIC EVALUATION
may have some symptoms of ASD Children with language delay or Children with a diagnosis of ASD
without meeting diagnostic criteria inattention to language should have should be assessed for potential
for the disorder. an evaluation of their hearing as part etiology and common coexisting
of their initial evaluation.99 Hearing medical conditions. At the time of the
Language Testing loss may co-occur with ASD and 2007 AAP clinical reports on autism,
Inherent in the core symptoms of ASD needs to be considered in children karyotype and DNA testing for fragile
are differences in the use of verbal with language delays, behavior X syndrome were the state-of-the-art

etiologic investigations. Soon TABLE 7 Potential Benefits of Establishing a Genetic Etiologic Diagnosis
thereafter, chromosomal microarray • Improving accuracy of counseling provided to patients and families:
(CMA) was endorsed by the American o Prognosis or expected clinical course
College of Medical Genetics and o Recurrence risk for the family and the individual affected
• Providing condition-specific family support, such as:
Genomics and the American Academy
o Improving psychosocial outcomes for patients and their families (eg, knowledge and sense of
of Child and Adolescent Psychiatry as empowerment, parental quality of life)
the most appropriate initial test for • Preventing morbidity and treating medical conditions associated with the genotype, such as:
etiologic evaluation of children with o Conditions or anomalies likely to be present at diagnosis
ASD.76,107–110 Despite rapid o Conditions that may develop later
• Refining treatment options, including:
technological advances in
o Avoiding therapeutic interventions that may be based on unfounded etiologic theories
neuroimaging and other areas, many o Avoiding ineffective or potentially harmful treatments
of the recommendations for clinical o Providing access to emerging etiology-specific treatments
evaluation published in 2007 are • Facilitating acquisition of needed services and access to research treatment protocols
unchanged. This section summarizes • Avoiding additional diagnostic tests, which may be unnecessary, expensive, and/or uncomfortable
recent advances in understanding the Adapted from Sun F, Oristaglio J, Levy SE, et al. Genetic Testing for Developmental Disabilities, Intellectual Disability, and
Autism Spectrum Disorder. Rockville, MD: Agency for Healthcare Research and Quality (US); 2015; Amiet C, Couchon E,
etiologies of ASD and how they
Carr K, Carayol J, Cohen D. Are there cultural differences in parental interest in early diagnosis and genetic risk
translate into recommendations for assessment for autism spectrum disorder? Front Pediatr. 2014;2:32; Srivastava S, Cohen JS, Vernon H, et al. Clinical
clinical practice. whole exome sequencing in child neurology practice. Ann Neurol. 2014;76(4):473–483; Iglesias A, Anyane-Yeboa K, Wynn J,
et al. The usefulness of whole-exome sequencing in routine clinical practice. Genet Med. 2014;16(12):922–931; Lingen M,
Albers L, Borchers M, et al. Obtaining a genetic diagnosis in a child with disability: impact on parental quality of life. Clin
Medical Workup of the Child With ASD Genet. 2016;89(2):258–266; Riggs ER, Wain KE, Riethmaier D, et al. Chromosomal microarray impacts clinical manage-
Genetic Testing ment. Clin Genet. 2014;85(2):147–153; and ACMG Board of Directors. Clinical utility of genetic and genomic services:
a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015;17(6):505–507.
Advances such as the development of
CMA and next-generation sequencing
physical examination should include abnormalities.109 Genetic evaluation
technologies and the application of
assessment of growth relative to should be recommended and offered
these technologies to well-
typical curves (including head to all families as part of the etiologic
characterized patient cohorts have
circumference), dysmorphic features, workup. A stepwise general approach
led to progress in the understanding
organomegaly, skin manifestations of is provided in Table 8 as a practical
of the complex genetics of ASD and
neurocutaneous disorders (eg, guideline.110,120 The presence of
other neurodevelopmental disorders
tuberous sclerosis and dysmorphic features or intellectual
in the last decade. Identifying
neurofibromatosis), and neurologic disability is generally associated with
a genetic etiology provides clinicians
with more information for families
about prognosis and recurrence risk TABLE 8 Genetic Etiologic Investigations in Patients With ASD
and may help to identify and treat or
Step Genetic Etiologic Investigations
prevent co-occurring medical
conditions, guide patients and 1 Consider referral for pediatric genetics evaluation
2 Comprehensive history (including 3-generation family history with emphasis on individuals with
families to condition-specific ASD and other developmental, behavioral and/or psychiatric, and neurologic diagnoses)
resources and supports, and avoid Physical examination (including dysmorphology, growth parameters [including head
ordering unnecessary tests circumference], and skin examination)
(Table 7).111–117 Most parents find • If syndrome diagnosis or metabolic disorder is suspected, go back to step 1 (genetics and/
this information to be useful.118 As or metabolism referral) and/or order the appropriate targeted testing
• Otherwise, proceed to step 3
research progresses, genetic testing 3 Laboratory studies
may contribute to identifying • Discuss and offer CMA analysis
effective interventions related to • Discuss and offer fragile X analysis; if family history is suggestive of sex-linked intellectual
specific etiologies. disabilities, refer to genetics for additional testing
• If patient is a girl, consider evaluation for Rett syndrome, MECP2 testing
Etiologic investigation begins with • If these studies do not reveal the etiology, proceed to step 4
a careful medical, developmental- 4 Consider referral to genetics, workup might include WES
behavioral, and family history and Adapted from Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation
a thorough physical and neurologic in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15(5):399–407;
Srivastava S, Love-Nichols JA, Dies KA, et al; NDD Exome Scoping Review Work Group. Meta-analysis and multidisciplinary
examination.109 The history should consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental
include potential prenatal exposure to disorders [published online ahead of print June 11, 2019]. Genet Med. and Shevell M, Ashwal S, Donley D, et al; Quality
teratogens (such as medications, Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society.
Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Sub-
alcohol, drugs) and other factors that committee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology.
increase risk for ASD.109,119 The 2003;60(3):367–380.

increased likelihood of finding individuals with ASD are provided in have consistently been used to
a genetic abnormality.121 However, Supplemental Table 14. identify a molecular diagnosis in 26%
authors of some clinical studies have to 29% of individuals for whom
Because fragile X syndrome increases
identified similar yield for genetic neurodevelopmental disorders were
risk for ASD, DNA testing for fragile X
testing in children without these risk the primary indication for
syndrome should be recommended
factors.122,123 testing.143–145 Authors of studies of
for all children with ASD, but
clinical populations with ASD have
In some cases, individuals with especially for boys and children with
reported diagnostic yields of 8% to
clinical genetic syndromes, such as a suggestive family history of male
20%.121,144 The yield of WES is
fragile X syndrome, tuberous sclerosis members with intellectual disability.
higher when both the parents and the
complex, and others (such as those Physical examination might reveal the
child who is affected are evaluated144
described in Supplemental Table 13), common features of a large head size,
to allow for comparison of the child
also meet criteria for ASD.124,125 prominent jaw, large ears,
with parents who are unaffected.
When a specific syndrome or ligamentous laxity, and, in male
metabolic disorder is suspected, the patients, large testes after puberty. Some geographic areas may have
clinician should proceed with the The cytosine-guanine-guanine limited availability of pediatric
appropriate targeted testing or trinucleotide repeat expansion that is subspecialists (eg, in genetics or
referral to a pediatric geneticist or responsible for fragile X syndrome is metabolism) who can guide the
neurologist. For example, a girl with not detected on CMA and must be genetic workup, so primary care
significant developmental delays, ordered as a separate test. The providers may be in the position to
deceleration in head growth velocity, current estimate is that consider and direct etiologic
and characteristic midline hand approximately 0.45% of individuals evaluation. The complexity of genetic
movements should prompt genetic with ASD have the full mutation for testing is such that most primary care
testing for a mutation or deletion or fragile X syndrome, and many of them providers may want to consult with
duplication of MECP2, the gene are female.130,132,135–137 Because a specialist to plan testing and
implicated in Rett syndrome.109,126 fragile X syndrome testing is interpret results. The clinical etiologic
Another specific example would be relatively inexpensive and the evaluation should be tailored to the
a boy with ASD with marked condition has important genetic individual patient, taking into
macrocephaly and pigmented counseling implications, it is consideration information from
macules on the penis, findings that reasonable to consider testing both the history and physical
would warrant sequencing and male and female patients with ASD, at examination109,110 and the values and
deletion or duplication analysis of the least until more data become wishes of the family. The stepwise
PTEN gene.127 Descriptions of these available to clarify the issue. general approach summarized in
and other clinical syndromes Table 8 can be used to guide this
When the history and physical
associated with ASD are provided in process.
examination, CMA, and fragile X
Supplemental Table 13.
analysis do not identify an etiology, It is important for families to
CMA is recommended if the etiology the next step at this time in the understand that genetic tests may
for developmental disability is not etiologic evaluation for ASD is whole- explain the cause of their child’s ASD
known. CMA identifies copy number exome sequencing (WES). WES or provide information about the
variants (CNVs) at this time, which technology allows for the statistical risk of ASD, but they are
are DNA duplications or deletions identification of single-nucleotide not diagnostic of ASD; the diagnosis
that alter the function of genes variants, including pathogenic loss-of- of ASD is made on the basis of clinical
(Table 8, step 2). CMA reveals function mutations and missense symptoms. Unlike CMA and WES,
a definitively pathogenic CNV mutations, which have been found to commercially marketed tests may not
in 5.4% to 14% (median 9%) of be associated with ASD.138–142 have the potential to provide
individuals with ASD in clinical Examples of ASD risk genes identified a molecular etiologic diagnosis.
samples.121,128–135 When CNVs of or confirmed in WES studies are Genomic testing technology is
uncertain significance are included, provided in Supplemental Table 15. evolving rapidly, as is our
approximately 17% to 42% of As with other tests, clinicians understanding of the genetic
patients with ASD have findings on ordering this test should be familiar architecture of ASD, and these
the CMA. Some of the variants of with both pretest counseling and recommendations for testing will
uncertain significance may be interpretation of the results. A genetic need to be updated as new studies
determined as pathogenic in the counselor is helpful in explaining the are published.146 For example, it is
future. The most commonly identified reason for testing as well as the anticipated that CMA and WES will
recurrent pathogenic CNVs among results. Large clinical WES studies soon be combined because of

improvements in accurate require intervention.159,160 The need metabolic conditions that may be
identification of CNVs using sequence for clinical MRI should be directed by associated with an ASD phenotype
data and that sequencing of the a history and physical examination. are provided in Supplemental
exome will be replaced by sequencing MRI may be indicated in the Table 16. There is no evidence at this
of the entire genome as issues with evaluation of atypical regression, time for routine testing of hair, blood,
interpretation and cost become more microcephaly, macrocephaly, seizures, or urine for environmental toxins or
manageable.121,130,147–150 intracranial manifestations of genetic heavy metals outside of laboratory
disorders, abnormal neurologic screening for lead exposure.169
Parents of a child with ASD should be
examination, or other clinical
counseled regarding recurrence risk
indications.76,109,161,162 Imaging EEG
in subsequent offspring, and the
technology used to examine brain Children with ASD have an increased
nature of the counseling depends
structure and function provides risk for seizures, and EEG
greatly on whether a specific genetic
valuable insight into the neurobiology abnormalities are common in the
cause of the child’s ASD has been
of ASD in research settings and may absence of clinical seizures (see
identified. When a specific genetic
lead to useful clinical applications in Seizures section for more
etiology has been determined, the
the future. information).170–175 However, EEG is
family can be provided with
information about the risk of Metabolic Testing not recommended as a routine
recurrence in subsequent offspring. baseline evaluation in the absence of
The yield of routine metabolic testing clinical concern about seizures,
However, when genetic testing has
for children with ASD is low and not atypical regression, or other
not been completed or has not
recommended for regular use.163–167 neurologic symptoms on history or
revealed the etiology of the child’s
However, large population-based examination that would suggest an
ASD, recurrence risk counseling is
studies are lacking, so accurate EEG is indicated.161,170,172,176 Late or
based on group averages derived
prevalence and diagnostic yield atypical loss of language, as might be
from the existing literature. For
estimates are not available. Metabolic observed in electrical status
a couple with 1 child with ASD of
workup should be informed by epilepticus of sleep with loss of
unknown cause, the current best
history, family history, symptoms, and language, should be evaluated with an
estimate of recurrence in
examination and might include overnight EEG.161,170,172,176 Primary
a subsequent child is approximately
measurement of fasting plasma amino care clinicians should discuss the
10% (range 4%–14%151–153). If
acid levels, urine organic acid levels, increased risk and the signs and
a couple already has $2 children with
and acylcarnitine metabolite levels symptoms of seizures with the
ASD of unknown etiology (idiopathic),
and other testing for specific families of children diagnosed with
the chance of a subsequent child
metabolic disorders. History of ASD, maintain a high index of clinical
having ASD may be as high as 32% to
atypical regressions (later than suspicion for seizures, and consult
36%.151,154 However, the risk is not
2 years of age, motor regression, or with a pediatric neurologist when
limited to ASD. Siblings of children
multiple regressions), family history concerned about atypical regression
with ASD who do not have ASD
of early childhood death or diagnosed or the possibility of seizures.170,172,176
themselves may have a 20% to 25%
metabolic disorders, and physical
risk for language disorders and other
features, such as significant hypotonia
neurodevelopmental and psychiatric The Biology of ASD
or weakness, visual and hearing
disorders.152,155,156 Genetics and ASD
impairment, and dysmorphic
features, would suggest consultation ASD is clinically and etiologically
Neuroimaging with a specialist to guide evaluation heterogeneous yet highly heritable.
Specific clinical neuroimaging for metabolic or mitochondrial The rate of ASD in siblings is much
findings are not more prevalent in disorders.109,168 Children who higher than the rate in the general
ASD compared with other present with motor delay should be population. Twin studies demonstrate
neurodevelopmental disorders, nor evaluated with creatine kinase substantially higher concordance
do specific abnormalities correlate and thyroid-stimulating hormone rates for symptoms of ASD in
with clinical, etiologic, or testing, according to AAP monozygotic twins than in dizygotic
pathophysiological aspects of recommendations.9,49 Although twins.177 A meta-analysis involving
ASD.120,157,158 Incidental findings are metabolic disorders are uncommon 6413 twin pairs revealed a 98%
common in neuroimaging studies causes of ASD, the potential impact is concordance in monozygotic twins,
obtained in the workup of children high because treatment may be a 53% to 67% concordance in
diagnosed with ASD but rarely available and the inheritance pattern dizygotic twins, and heritability
provide etiologic information or may be known.109,124 Examples of estimates from 64% to 91%.177,178

Siblings may also be at risk for intracellular signaling, transcription Genes, Immunologic Exposures, and ASD
symptoms related to ASD that do not regulation, and chromatin It has been proposed that children
meet the threshold for a diagnosis of remodeling.139,190,191,196 It is with ASD-associated CNVs may be
ASD and have been described as the important to note that no specific more susceptible to environmental
broader autism phenotype.141,179 mutation has been identified that is insult in the form of maternal
These data provide strong evidence unique to ASD; there is substantial immune activation. Report of
for a genetic contribution to ASD genetic overlap between ASD and maternal infection or fever during
risk.180–184 other neurodevelopmental disorders, pregnancy may be associated with
including intellectual disability, increased severity of ASD-related
Risk for ASD also is increased in the
epilepsy, and schizophrenia.197–204 symptoms in offspring who are
children of both older fathers and
older mothers.185–187 The increased affected.217 The pathogenic role of
risk with parental age may be related Genes, Environmental Exposures, and circulating maternal antibodies
to germline mutations in older ASD directed to fetal brain tissue and the
fathers.143,188 Mechanisms mediating potential value of maternal antibody
The potential environmental factors panels as biomarkers of ASD are
the effect of advancing maternal age
that may be related to increased currently being studied.218–222 Unless
on ASD risk are less clear.143
reported prevalence of ASD is an area otherwise indicated (eg, history
Increased maternal and paternal age
of active study that, as yet, is without suggestive of autoimmune or
are independently associated with
firm conclusions.119 Environmental immunologic disorder), no immune
ASD risk, and a joint effect seems to
factors associated with ASD include in
occur as well.185–187 testing is recommended in the
utero exposure to medications such etiologic workup of a child with ASD.
Important aspects of the genetics of as valproate and thalidomide. Other
ASD are still poorly understood, prenatal influences, such as short
including the role of common interpregnancy interval, multiple Epigenetics
variants, epistasis (gene-gene gestation, maternal obesity, Epigenetic modifications, such as
interactions), and environmental gestational bleeding, gestational DNA methylation and
modification of genotype effects. In diabetes, advanced parental age, and posttranslational histone
contrast, advances such as CMA and infections (eg, rubella and modification, produce heritable
next-generation sequencing cytomegalovirus), may be associated changes in gene expression that do
technologies have resulted in with increased risk for ASD.205–209 not involve a change in the DNA
identification of large-effect Perinatal factors, such as preterm sequence. Some genetic disorders
(pathogenic) rare variants that birth, low birth weight, fetal growth associated with ASD (eg, Rett
appear to be causally associated with restriction (ie, small for gestational syndrome; CHARGE syndrome; 15q
ASD, including CNVs, which are age), intrapartum hypoxia, and duplication; Angelman syndrome; and
deletions or duplications $1000 bp neonatal encephalopathy, are fragile X syndrome), involve genes
in size that alter the dosage of genes, associated with increased ASD that either encode epigenetic
and sequence-nucleotide risk.205,210–212 Environmental factors regulators or are sensitive to
variants.189–192 Pathogenic rare may present independent risk to alterations in their epigenetic
variants may arise de novo or be prenatal brain development or may regulation.223,224 Because epigenetic
inherited as autosomal dominant, affect gene function in individuals modifications can be influenced by
autosomal recessive, or X-linked with genetic predisposition.213 environmental factors, such as
mutations. Researchers of CMA and Population-level associations with prenatal maternal exposures and
WES studies have established that ASD have been examined for postnatal experience, they represent
although de novo and inherited rare organophosphates and certain other 1 interface between genes and
variants of large effect size are pesticides, metals, volatile organic environment. However, epigenetic
collectively common, no individual compounds, and air pollution, modifications are not the only
pathogenic variant accounts for more particularly particulate matter and mechanisms by which gene
than 1% of cases of ASD.* Genes that nitrogen dioxide.214–216 Research on expression is regulated, and
contribute to ASD are involved in environmental exposures may be of epigenetics should not be conflated
a variety of biological functions, with great importance in identifying with the broader category of
convergence on aspects of brain modifiable risk factors related to ASD environmental effects.223,225
development and function, including and other developmental disorders. It Currently, the evidence that alteration
synaptic structure and function, is prudent to limit exposure of of gene expression by environmental
children and pregnant women to factors plays a causal role in ASD is
* Refs 121, 144, 189–195. known neurotoxicants. very limited.223–228 Investigation of

the role of epigenetic and other Brain Structure and ASD: Early Brain Overgrowth
nongenetic modifications that Neuropathology
Cross-sectional and longitudinal
alter gene activity without Neuropathological research has been studies suggest that as a group,
changing the DNA sequence is an limited by the small number of children later diagnosed with ASD
active area of etiologic research postmortem brains available for may have an average or below-
in ASD. study. Developmental brain average head circumference at birth,
abnormalities in people with ASD are with an acceleration in brain growth
Vaccines reported in the cerebral neocortex; before 2 years of age.256 This rapid
limbic system structures, including brain growth leads to significantly
The scientific literature does not the hippocampal formation and above-average head circumferences
support an association of amygdala; basal ganglia; thalamus; and MRI brain volumes in toddlers,
vaccination as an environmental brainstem; and cerebellum. These followed by a plateau in brain growth,
factor that increases the risk for brain abnormalities include dysplasia, with brain volumes in adolescence
ASD. Children with ASD should be altered neurogenesis, and abnormal and adulthood similar to those of
vaccinated according to the neuronal migration.249–251 The vast controls.257,258 Almost 16% of young
recommended schedule. majority of abnormalities described children with ASD have a head
Epidemiological studies do not originate during prenatal brain circumference greater than the 97th
demonstrate any association of the development.249,251,252 Findings in percentile.258 A preliminary study
measles-mumps-rubella vaccine, the cerebral cortex may include focal suggested that infant siblings of
mercury exposure by thimerosal- disruption of neuronal migration, children with ASD who exhibited
containing vaccines, aluminum in minicolumnar abnormalities, and a larger head circumference at
vaccines, or increased level of variations in neuronal 12 months and showed more slowing
immunologic exposure attributable density.249,251,252 A decreased of head circumference growth from
to a larger number of vaccines number of Purkinje cells in the 12 to 24 months had an increased
(either given at 1 time or cerebellum is 1 of the most chance of demonstrating symptoms
cumulatively) with ASD.214,229–246 consistently reported of ASD.259,260 Although this finding
Vaccines used for children in the neuropathologic findings associated raises the possibility that patterns of
United States have not contained with ASD. Although it was initially brain growth might be used for early
thimerosal since 2001. The authors thought to be of prenatal onset, identification, the rate of head growth
of a 2012 Cochrane review234 and evidence now indicates that this did not predict which infants
a 2014 quantitative meta-analysis phenomenon is more likely to be an developed ASD in the first 3 years of
of pooled data from cohort studies acquired process that occurs life in a large prospective study of
involving 1 256 407 children and postnatally, potentially related to high-risk infants.261 It is possible that
case-control studies involving 9920 seizures, medications, and/or a large head size is unrelated to ASD
children reviewed the scientific ischemia near the time of death or and/or may be part of general
literature and came to this factors other than ASD.249 No uniform somatic overgrowth.262–265
conclusion.231 Evidence implicating neuropathology has been identified in
immunizations as a “second hit” people with ASD.
conferring ASD risk in genetically Neuroimaging Patterns Associated
susceptible subgroups is lacking. It With ASD in Research Studies
has been shown that the measles- Biomarkers Although there are conflicting
mumps-rubella vaccine is not Objectively measured biological findings, structural MRI volumetric
associated with increased risk for characteristics, or biomarkers, of ASD studies suggest that young children
ASD, even among children who are could potentially be used to predict with ASD differ from controls in total
already at higher risk because of ASD risk, enhance screening, and brain volume, cortical gray and white
having an older sibling with ASD. 229 permit presymptomatic detection. matter volume (particularly frontal,
Media coverage of vaccine issues Their use could improve the temporal, and cingulate cortices),
may inflate the perception of reliability and validity of clinical extraaxial cerebral spinal fluid
uncertainty by equal coverage of diagnosis (identifying clinically volume, and amygdala volume.266–271
vaccine proponents and opponents. meaningful subgroups that would A research-level analysis also has
The overwhelming weight of allow for prediction of prognosis or identified asymmetries in multiple
evidence supports vaccine safety. 247 treatment response), identify brain structures in people with
Communicating information about mechanisms for developing ASD.272 Diffusion tensor imaging has
vaccine safety is a critical treatment, and confirm the need for been used to identify altered patterns
component of pediatric practice. 248 a specific intervention.221,253–255 in white matter by 6 months of age in

infants later diagnosed with Other Potential Biomarkers repetitive behaviors and interests)1
ASD.270,273 Functional MRI has Although some studies have and co-occurring associated
demonstrated differences in people attempted to differentiate people impairments292-294; (2) maximize
with ASD relative to controls in with and without ASD on the basis of functional independence by
efficiency of visual processing, differences in laboratory profiles of facilitating learning and acquisition of
executive function, language, and platelet serotonin, plasma melatonin, adaptive skills; and (3) eliminate,
basic and complex social processing urine melatonin sulfate, redox status, minimize, or prevent problem
skills.274,275 Functional MRI in placental trophoblast inclusions, and behaviors that may interfere with
research settings demonstrate immune function, currently no functional skills.6,295,296 Treatments
differences in the mechanisms of diagnostic laboratory tests have been should be individualized,
attention to social stimuli, approved for ASD.286,287 To date, developmentally appropriate, and
modulation in response to task none of these potential biomarkers intensive, with performance data
demands or intensity of stimuli, under study has sufficient evidence to relevant to treatment goals to
and executive function in people be recommended. evaluate and adjust intervention.6,297
with ASD.274 Functional All interventions should be based on
underconnectivity has also been Biomarkers: Future Directions sound theoretical constructs, rigorous
demonstrated across a wide variety Proposed biomarkers for ASD risk methodologies, and objective
of the brain regions that support include genetic and biochemical scientific evidence of effectiveness.
language, executive function, findings in blood, urine, or brain Since the publication of the 2007 AAP
social cognition, emotion tissue; placental pathology; maternal clinical reports on autism,
processing, and motor tasks, autoantibody profiles; structural and a substantial published literature has
especially for long-range, frontal- functional MRI patterns; examined the effectiveness of
posterior networks.274,276,277 electrophysiological test results on interventions.48,295,297,298 Legal
EEG, including event-related mandates in education law in the
Electrophysiologic Testing and United States, which include the
Measurement of Eye Tracking potentials; responses in eye tracking;
and physical parameters such as head Individuals with Disabilities
Electrophysiologic research studies circumference growth trajectory. Education Improvement Act of 2004
demonstrate differences in auditory Although none of these proposed (IDEA) (Public Law 108–446) and the
processing (including language biomarkers has demonstrated No Child Left Behind Act of 2001
processing), visual processing sufficient predictive validity for (Public Law 107–110) and its
(including face processing), clinical use at this time,221,253–255,288 successor, the Every Student Succeeds
somatosensory response, the search for biomarkers is a major Act of 2015 ( Public Law 114–95),
multisensory integration, research focus. Biomarker research require the use of practices supported
attentional shifting, selective has important ethical issues,253 and by scientifically based research (IDEA
attention, recognition memory, and concerns have appropriately been and the No Child Left Behind Act of
neural connectivity in people with raised regarding premature 2001) or evidence-based practices
ASD.278–281 Continuous measures translation of research data into (Every Student Succeeds Act of 2015)
of resting-state and task-related commercially available tests (https://www.ed.gov/). Early
quantitative EEG are used to marketed to patients and intervention services under part C of
calculate and describe spectral families.221,253,289,290 However, the IDEA provide for assessment and
power, complexity, and coherence. capabilities to screen large numbers intervention for children younger
Although promising, the clinical of bioactive compounds, examine the than 3 years with developmental
utility of these measures as entire genome, and simultaneously delays, including ASD.
biomarkers requires additional analyze large data sets have
study.279 Eye tracking has been accelerated research into the Interventions for children with ASD
used to determine if infants who neurobiology of ASD and may result are provided through educational
are younger siblings of children in the identification of valid practices, developmental therapies,
with ASD and, therefore, biomarkers.221,255,291 and behavioral interventions.
at increased risk for ASD exhibit Treatment strategies may vary by the
differences in fixation on faces.282-284 age and strengths and weaknesses of
Preliminary evidence suggests SECTION 5: INTERVENTIONS the child. For example, intervention
that infants later diagnosed with The goals of treatment of children for a toddler with a recent diagnosis
ASD exhibit a decline in gaze with ASD are to (1) minimize core of ASD may include behavioral and
fixation from age 2 to age 6 deficits (social communication and developmental approaches
months.285 interaction and restricted or (individually or in the context of

comprehensive approach) and, as he Wong et al295 described 2 categories promoted. These interventions are
or she progresses, involvement in of evidence-based interventions, the provided in a structured setting by an
a specialized or typical preschool comprehensive treatment model adult, in naturalistic environments
program. For older children, (CTM) and focused interventions. with peers, or as a component of
intervention is more likely to occur in These interventions may be provided a more comprehensive approach.295
educational settings, with integration in different settings (eg, the home, Focused interventions may be
of behavioral and developmental classroom, naturalistic environment, effective for promoting skill
therapies to promote skill or community), by different providers development and
development. In addition to variation (eg, developmental specialist, communication.295,297,304,305
by age of the child, interventions behavioral therapist, educator, or Pediatricians may be asked to advise
differ in theoretical approach and trained parent), individually or in families on therapy choices or write
scope (eg, focused and targeted or group settings, and by using a set prescriptions for therapies.306 It is
comprehensive), settings and/or curriculum or guide. helpful for clinicians to have an
modality of delivery (eg, individual understanding of intervention
versus group or classroom, delivered The CTM uses a central conceptual
framework to address a broad array terminology and of the evidence base
by a professional versus a trained so they can effectively communicate
parent, and school versus home of symptoms and is designed to
address specific skill(s) or the rationale for medically indicated
setting), and targets of treatment recommendations with
intervention.48,297 Interventions may symptom(s). A CTM should be
replicable, intense, and designed to families, educators, therapists, and
be provided through public and/or other service providers as well as
not-for-profit agencies, schools, and address multiple therapeutic goals
over a period of time. Provision of with insurance companies, health
early intervention services, and some care administrators, funding agencies,
may be paid for through insurance.299 services may occur in individual
instruction or class settings and policy makers.295
Families should be involved in the
selection of intervention approaches (specialized or inclusive), should This report describes various types of
and remain an involved participant in include parents, and may involve interventions provided for children
technology-assisted intervention.303 and youth with ASD. Additional
subsequent educational and
therapeutic decisions. There is research is needed to evaluate the
Applied behavior analysis (ABA),
regional variation in the availability of effectiveness of current approaches
developmental approaches, and/or
various types of therapy and and develop interventions that
naturalistic approaches may be used
providers that sometimes results in address core deficits of ASD. At the
in CTMs.303 Examples of CTMs
long waits for service, less-than- time of diagnosis, parents of young
include early intensive behavioral
desired intensity, or inability to preschool children may ask their
intervention, Treatment and
obtain a desired intervention provider to help them decide what
Education of Autistic and Related
altogether. By law, students with ASD type of intervention they should elect.
Communication-Handicapped
should receive an appropriate Two common theoretical approaches
Children (TEACCH), and the Early
educational program, although it may to intervention for symptoms of ASD
Start Denver Model (ESDM).295,303
not include all of the components are ABA and developmental
desired by the family. Advocacy is Focused intervention practices are models.296–298,307 Although these
often necessary to obtain desired designed to address a single or approaches have important
services through schools or through limited range of skills, such as distinctions, they also have significant
mechanisms paid for by insurance. It increasing social communication or overlap, and interventions
is noted that many of the learning a specific task, and may be increasingly are incorporating aspects
interventions in common use do not delivered over a short period of of both. There is considerable
have a strong evidence base. Some time.295,297,303 Focused intervention regional variation in the availability of
types of intervention may not be paid practices may be behavioral, various interventions. Table 9
for by insurance. developmental, and/or educational. describes common characteristics of
Focused interventions may be empirically supported
Systematic reviews of the evidence grounded in principles of ABA, in interventions.296,297,308,309
base for treatment have been which specific skills are taught in
Approaches to Intervention
completed on early intensive a stepwise progression by using
intervention,44,300 medical principles of reinforcement or ABA
treatments,301 behavioral developmental theory, in which the Most evidence-based treatment
interventions,294,298 and evidence- emerging skills inherent in models are based on principles of
based practice guidelines.292,302 neurobehavioral maturation are ABA. ABA has been defined as “the

TABLE 9 Characteristics of Effective Interventions
Features of Practice Common Characteristics of Empirically Supported Interventions
Assessment and goals Systematically assess skills
Include input of family (shared decision-making)
Select individualized measurable goals and instructional procedures on the basis of objective assessment of each child
Use assessment-based, empirically supported instructional methods to build, generalize, and maintain skills and reduce problem
behaviors
Instructional methods Address core symptoms in social communication and restricted and repetitive behaviors as well as skill deficits
Provide a student/teacher ratio low enough to address the child’s individualized goals
Interventions should be by providers who are properly trained and should maintain fidelity with the treatment approach selected
Ensure that multiple providers work collaboratively
Services and supports Individualize services and support
Make use of the child’s interests and preferences in determining reinforcement systems
Incorporate preferred activities to increase engagement in activities
Environment Provide a structured learning environment that helps children anticipate transition between activities, including a predictable routine
and visual activity schedules
Organize workspaces to minimize distraction and promote task completion
Limit access to things that may distract a student
The environment should promote opportunities for the student to initiate communication and interact with peers
Behavioral Implement a functional behavioral analysis to identify the reasons why challenging behaviors occur and develop a behavior
management improvement plan based on this assessment (IDEA-mandated approach)
Teach children more appropriate responses using the behavior improvement plan
Progress Systematically measure and document the individual child’s progress
Adjust instructional strategies as necessary to enable acquisition of target skills
Family support Involve and educate families so they can use the behavioral strategies at home and in the community
Transition planning Plan for transitions in school settings and to adulthood (eg, from home-based early intervention to preschool services, preschool to
elementary school, elementary school to middle school, middle school to high school, high school to work or postsecondary
education, and home to community living)
Adapted from Smith T, Iadarola S. Evidence base update for autism spectrum disorder. J Clin Child Adolesc Psychol. 2015;44(6):897–922; Myers SA, Pipinos II, Johanning JM, Stergiou N. Gait
variability of patients with intermittent claudication is similar before and after the onset of claudication pain. Clin Biomech (Bristol, Avon). 2011;26(7):729–734; and Myers SM.
Management of autism spectrum disorders in primary care. Pediatr Ann. 2009;38(1):42–49.
process of systematically applying environments that may be child led intensive behavioral intervention, is
interventions based upon the and implemented in the context of supported by a few randomized
principles of learning theory to play activities or daily routines and controlled trials (RCTs) and
improve socially significant behaviors activities and are altered on the basis a substantial single-subject
to a meaningful degree, and to of the child’s skill development (eg, literature.297 When only RCTs are
demonstrate that the interventions pivotal response training, reciprocal considered, few interventions have
employed are responsible for the imitation training, and sufficient evidence to be endorsed
improvement in behavior.”310 The use others).297,309,312,313 To determine either for children younger than
of ABA methods to treat symptoms of what intervention is most 12 years298 or for adolescents.314
ASD suggests that behaviors exhibited appropriate, the behavioral clinician
Children younger than 12 years
can be altered by programmatically works with the family and child to
receiving more hours per week of
reinforcing skills related to determine which skills to target for
ABA were found to be more likely to
communication and other skill development and maintenance and
achieve the individualized goals
acquisition.311,312 Thus, ABA what goals are appropriate.
identified in their programs.315 In
treatments may target development
ABA programs are typically designed retrospective studies, more intense
of new skills (eg, social engagement)
and supervised by professionals ABA therapy was associated with
and/or minimize behaviors (eg,
certified in behavior analysis. The achieving optimal developmental
aggression) that may interfere with
majority of states at this time have outcomes.316 Given the heterogeneity
a child’s progress.
licensure for board-certified behavior of the ASD phenotype, the service
analysts with provisions for payment needs of children, youth, and adults
ABA interventions vary from highly
by insurance. ABA may be prescribed need to be individualized by using
structured adult-directed approaches
or recommended by a physician or available clinical data.
(eg, discrete trial training or
licensed psychologist.
instruction, verbal behavior In some instances, a behavioral
applications, and others) to A comprehensive ABA approach for intervention is needed to address
interventions in natural younger children, also known as early acute serious problem behaviors that

must be given priority, for example, Relationship-Based model). In 1 RCT a clinical measure of social behavior
because of safety issues.295 Whether comparing parent coaching using this through an early intervention
a student is getting formal ABA under approach to community intervention program.327
IDEA or not, a family can request that alone (N = 112) in children ages 2 to
challenging behaviors be evaluated in 5 years, parents who were taught this Combined Approaches
the school setting by using behavioral approach were less directive, and Common factors in combined
principles through a functional their children were rated as more developmental and behavioral
behavioral assessment. The target socially responsive, although IQ and approaches include use of principles
symptoms to treat may then be language scores were no different of ABA to reinforce skill building;
divided into component parts that are between groups, and half of the a systematic approach with a manual
addressed in a stepwise fashion (task children in the control group for training practitioners who would
analysis).313,317 Once the reasons for improved in their affective ratings.323 use the intervention in a standard
the behavior are understood, A similar approach is relationship fashion; individualized treatment
a behavior improvement plan may be development intervention,324 and goals for the child and means of
implemented. more research is needed to evaluate measuring progress; child-initiated
efficacy and community use. teaching, imitation, and modeling;
Developmental Relationship–Focused and adult prompting that fades over
Interventions Naturalistic Developmental Behavioral time to promote independence.296 It
Intervention for young children also Intervention may be difficult to advise parents on
may be derived from developmental Naturalistic developmental specific programs in community
theory, which is focused on the behavioral interventions (NDBIs) settings because the way the program
relationship between the caregiver’s incorporate elements of ABA and is conducted may differ from the
level of responsiveness and the developmental principles, such as research settings.328 However, it is
child’s development of social emphasis on developmentally based always accurate to describe the
communication.296,318–320 Through learning targets and foundational common characteristics of empirically
interaction with others, children learn social learning skills, with delivery of supported interventions and
to communicate and regulate interventions in the context of recommend that families seek
emotions and establish a foundation naturally occurring social activities interventions that incorporate these
for increasingly complex thinking and within natural environments. They features (Table 9).
social interaction. Therefore, use child-initiated teaching episodes, Parent-Mediated Treatment or Parent
developmental models designed to naturally occurring opportunities for Management Training
promote social development in learning, and turn-taking interactions
children with ASD are focused on the within play routines and implement Increasing evidence reveals that
relationship between the child with ABA-based approaches to address focused interventions delivered by
ASD and his or her caregiver through measurable goals.296 trained parents or other caregivers
coaching to help increase can be an important part of
responsiveness to the adult (ie, the The most extensively studied NDBI a therapeutic program.297,329–332
interventionist or parent or approach is the ESDM, which More RCTs have been published on
caregiver) through imitating, prepares children to learn in parent-mediated therapies than on
expanding on, or joining into child- naturalistic environments.325 In other nonpharmacologic
initiated play activities. This approach a multisite trial of ESDM, early age at interventions. What is sometimes
may address core symptoms of entry to therapy and more hours of called parent management training is
ASD, such as joint attention, total therapy were associated with divided into 2 categories: parent
imitation, and affective social improved outcome.326 Of note, the 48 support and parent-mediated
engagement.296,297,321,322 children randomly assigned to ESDM interventions. Parent support
or community treatment in the interventions, which are knowledge-
Developmental models for original trial were studied by using focused and provide indirect benefit
intervention are focused on teaching event-related potentials and spectral to the child, include care coordination
adults to engage in nondirective power on EEG while viewing faces as and psychoeducation. Parent-
interactive strategies to foster opposed to objects and were mediated interventions, which are
interaction and development of compared with typical controls on technique-focused and provide direct
communication in the context of play. these tasks. This is an early benefit to the child, may target core
One such approach is known as demonstration of improvement on symptoms of ASD or other behaviors
DIRFloortime (The Developmental, a neurophysiologic measure or skills and may be built on ABA
Individual Differences, and associated with improvement on approaches in natural settings.331

Training sessions for caregivers may aged pupils in inclusive settings for environmental and behavioral
be delivered in the home, clinic, teaching social interaction.344–346 An supports.344 Research interventions
school, or other community RCT of 294 preschool-aged children may not be comparable with
settings or remotely by revealed that LEAP was associated community-provided school
telehealth.297,329–331,333–337 An RCT with improvement in socialization, programs. Future research is needed
involving 86 toddlers and their cognition, language, and challenging to address how best to provide
primary caregivers demonstrated that behavior and that LEAP was superior evidence-based intervention in
10 weeks of hands-on parent training to a treatment-as-usual method.345 classroom settings.
in joint attention, symbolic play,
TEACCH class settings are visually Education in the Least Restrictive
engagement and regulation (an NDBI)
organized to promote engagement Educational Environment
was superior to a parent-only
and learning.344 The TEACCH
psychoeducational intervention for Pediatricians have an important role
approach to skill acquisition includes
increasing joint engagement.338 A in advocating for children and youth
assessment-based curriculum
parent training approach may be used with special health care needs,
development and an emphasis on
to promote compliance with including ASD, in the educational
structure, including predictable
instruction, social communication, setting. Students have a right to a free
organization of activities and use of
and other identified goals of the and appropriate public education.
visual schedules, organization of the
caregiver, such as reducing Educational programs for school-aged
physical environment to optimize
maladaptive behaviors.331,339–342 children with ASD should promote
learning and avoid frustration (eg, by
Including parents in the intervention language, academic, adaptive, and
minimizing distractions and/or
process is critically social skills development and prepare
sensory dysregulation), and
important.43,326,343 them for postsecondary education or
adaptation and organization of
employment.348 Most, but not all,
materials and tasks to promote
Educational Interventions students with ASD will have some
independence from adult directions
Classroom-Based Models individualization of their education
or prompts.344,347 Instruction is
under the guidance of an IEP
It is the expectation that school-aged organized in a predictable fashion
determined by the school
children will be educated in and uses visual schedules with
multidisciplinary team in conjunction
classroom settings with supports for promotion of independence in
with the family. Others may receive
a broad effect on the symptoms of activities planned into the
accommodation and/or
ASD and associated deficits. instruction.347 This approach is
environmental modifications under
Educating students with ASD in the associated with a small, but
Section 504 of the Rehabilitation Act
least restrictive environment typically measurable, benefit in perceptual,
of 1973.349 A medical diagnosis of
requires an individualized program motor, verbal, and cognitive skills in
ASD alone does not automatically
that is modified to meet the students with ASD, with less
translate into eligibility for school-
Individualized Education Program measured effect on adaptive and
based services. Functional
(IEP) goals set by the family, student, motor function347 and challenging
impairment that affects participation
and school team. Some students who behaviors. Rigorous studies of
in the typical curriculum is required
do not qualify for an IEP by educational interventions for
to qualify for supports in the
educational criteria may be students with ASD at school age and
educational setting and may lead to
supported with accommodations beyond are necessary to understand
an IEP for the educational handicap of
through a Section 504 plan or with the effectiveness of different
autism. Most youth with ASD and
classroom-level accommodations. models.298
average-range intelligence will likely
Many students with ASD are educated
A comparison of the effects of LEAP require academic intervention
in inclusive classrooms with
and TEACCH classrooms with those of because of coexisting learning
supports. Other school-aged children
standard special education classes disabilities, executive function
and youth benefit from disorder-
taught by teachers familiar with ASD challenges, ADHD, motor processing
specific approaches. Examples of
revealed that the common features of deficits, the effects of their pragmatic
classroom-based models include
these interventions may be language differences on reading and
Learning Experiences and Alternative
responsible for improvements seen in writing, and/or challenges in
Programs for Preschoolers and their
all students. TEACCH was associated comprehension of spoken or written
Parents (LEAP) and TEACCH.344
with more reported improvement in language.350 Attention to the needs of
LEAP blends principles of ABA with ASD severity for students who had the individual student must be
special and general education greater cognitive delays. This finding central to the IEP process. Social skills
teaching techniques for elementary- may speak to the benefit of the of students with ASD may benefit

from students being in class and on skills support considered in their Because child-mediated interventions
the playground with peers with school and perhaps in other taught separately from social
typical development.351,352 However, therapeutic settings if settings have not had consistently
spending more than 75% of their indicated.351,354–356 Although families beneficial effects, interventions have
time in an inclusive educational identify the need to address social been developed for implementation
setting alone was not sufficient in skill developments in settings outside in the social settings that include
transition-aged youth to increase of school, the success of these types of peers, such as the classroom and
rates of college attendance, high interventions is variable. playground. These interventions
school graduation, or functional Interventions may be divided into demonstrate improved playground
ratings.353 How to best support adult-mediated (skill building with interaction between children with
students with ASD in the least the individual child), peer-mediated and without ASD and improved
restricted environment requires (skill building with the child and identification as friends by typical
further study. typically developing classmates), and peers.351 Peer-mediated intervention
mixed approaches. Child-directed for students with ASD have revealed
Social Skills Instruction social skills interventions are often improved social connectedness and
Social skills deficits may present delivered individually or in small reduced social isolation and provide
differently depending on language groups with other children with evidence to support the use of these
abilities, developmental level, and similar needs. Therapy may be interventions in the classroom and
age. Examples of social skills deficits provided in behavioral health settings playground. An evidence-based
include the following: to complement the social skills approach designed for group
interventions at school.
• challenges with entering, administration, the Program for the
sustaining, and exiting interactions; Education and Enrichment of
Interventions addressing social skills
• difficulty attending to, Relational Skills, may improve both
may increase the child’s knowledge
understanding, and using teacher-reported social functioning
of the cues for social behavior and
nonverbal and verbal social cues, and adolescent-reported social
teach strategies for social problem-
such as eye contact, facial solving. A popular method uses the cognition.358 Fewer studies are
expressions, and gestures; social narrative to help a child define available to guide programs to
promote social skills development
• difficulty in understanding the social context of an anticipated
for adults with ASD. However, the
“unwritten” social rules of the or experienced situation, put it in
perspective, and then develop Program for the Education and
environment;
statements on how it makes the child Enrichment of Relational Skills
• not understanding the perspective group model has been demonstrated
feel and on what to do in response to
of others; to improve social skills in young
the event and feelings.357 This
• struggling with negotiation, coached rehearsal strategy may be adults with ASD.359
compromise, and conflict included within other programmatic
resolution; and approaches. Implementation may Families should be counseled to
• problems with interactive play or use a cognitive behavioral include development of social skills
participation in leisure activities. intervention strategy in which the with discrete goals and interventions
child identifies feelings and thoughts in the IEP or educational plan as
The importance of caregiver well as to be cognizant of potential
and learns to substitute more
involvement in teaching social skills opportunities to promote social
socially appropriate alternatives.354
to preschool-aged children needs to interaction in the natural
Video- and computer-based social
be emphasized for families of young environment and in the context of
skill interventions may extend access
children with ASD. Reinforcing social other therapies.360 Implementing
to intervention once an evidence
interaction is central to the success of IEP goals across the day and
base is established. A systematic
evidence-based ABA, developmental, generalizing specific skills to
review of RCTs of social skills
and NDBI approaches.296,354 Teaching promote conversation and nonverbal
training for children aged 6 to
and coaching social interaction communication, such as providing
21 years revealed that interventions
involves both behavioral therapy and
improved social competence and eye contact, directing facial
speech and language therapy
friendship quality but did not result expressions, and using appropriate
approaches.
in differences in emotional gestures, is important, independent
School-aged children and adolescents recognition and social of age, and should involve both
with ASD, including those with typical communication. Transfer of skills to the caregivers and professionals.
academic skills, should have social other settings was inconsistent.356 More information about IEPs in

general can be found at http://www. onset of speech may be complicated individual is guided to
wrightslaw.com/info/iep.index.htm. by general delays in development communicate.369,370 This differs from
(intellectual disabilities) or coexisting AAC, in which the individual is taught
Other Therapeutic Interventions speech disorders, such as childhood to communicate independently.
Speech and Language Interventions apraxia of speech. Although using Future strategies to promote
Delayed language is an early concern communicative spoken phrases communication are expected to
for many children who are later before age 4 years is considered incorporate evolving knowledge
diagnosed with ASD. The a good prognostic sign for language about sensory processing and
communication symptoms included development in youth with ASD, connectivity of brain functions in
in the DSM-5 criteria for ASD reflect emergence of phrase speech may people with ASD.
core deficits in social communication occur to at least age 10 years,
Children and youth with ASD often
and interaction, such as failure of especially in children with preserved
have deficits in pragmatic language
back-and-forth communication, nonverbal skills and evidence of
that can affect social interaction with
deficits in nonverbal communication social engagement.364
adults and peers and academic
(such as eye gaze and use of gesture), When children do not spontaneously performance as more complex
difficulty adjusting behavior to suit speak, augmentative and alternative language becomes required for
the social context, and restricted and communication (AAC) may be reading comprehension and analysis
repetitive behaviors leading to introduced. Examples of AAC of information. In addition, literal
perseverative vocalization, echolalia, strategies include sign language, the interpretation of language and
and preoccupation with restricted Picture Exchange Communication difficulty in understanding the intent
topics of interest. All children with System, and speech-generating of other people leads to behavioral
ASD should have documentation of devices.365,366 The use of AAC may challenges in some people with ASD
specific coexisting speech and help promote social interaction and and affects success in school, leisure
language diagnoses so that understanding of the purpose of activities, and employment. School-
appropriate intervention might be communication and does not delay aged students with spoken language
provided. onset of speech. Indeed, it may should have their pragmatic language
Speech-language therapy is the most enhance emergence of spoken words assessed as part of their school-
commonly identified intervention by pairing nonverbal and verbal related reevaluations, with
provided for children with ASD.361 communication. consideration of pragmatic language
The strategies used by speech- testing if academic problems and
The Picture Exchange Communication
language pathologists to reinforce inattention are noted in the
System is used to build
sound repetition and word use in classroom. Interventions may include
communication through picture
children with typical development are individual and group approaches that
identification and exchange as
often initially used with young include teaching and practicing
communication. With training,
children with ASD. Such strategies conversation. The pediatrician may
pictures can be sequenced to build on
include reinforcement of speech refer the child for private speech-
communicaiton.367 Picture strips that
sounds and communicative acts, language therapy if he or she is not
sequentially explain medical
imitation of the sounds the child eligible for services in school or if
procedures, for example, take
makes, and exaggerated imitation and increased intensity of intervention is
advantage of this approach. Use of
slowed tempo.362 The literature speech-generating devices and
desired. Although the impact of
offers the most support for speech-language therapy on
programs that use AAC on digital
approaches with preverbal children structural language improvement has
tablets also are increasing. These
with ASD in which adult prompts are not been adequately studied,
devices provide acoustic feedback to
used for communication, prompt improvement in ratings of
the child, and touch-screen tablets are
fading, and reinforcement of their conversational competence by
relatively inexpensive and portable.
own attempts at communication. parents and of classroom learning
Medical providers are often asked to
Intervention in naturalistic settings skills by teachers supports the
justify the purchase of touch-screen
and involvement of caregivers may recommendation for social skills and
tablets or AAC devices. It cannot be
help reinforce the initiation of social language interventions for
assumed that the use of AAC alone
communication and functional use of students with ASD.371
will lead to functional oral
sounds, gestures, and words. communication without a therapeutic
A significant minority (up to 30%) of plan.368 Current scientific evidence Motor Therapies
individuals with ASD ultimately do does not support the use of facilitated Children with ASD may have low
not acquire verbal speech.363 Delayed communication in which a nonverbal muscle tone or a developmental

coordination disorder. Although the Sensory Therapies occupational therapist, to work with
ages for sitting and walking do not In 2012, the AAP published a clinical a child by using play and sensory
differ between children with ASD report, “Sensory Integration activities to reinforce adaptive
and children with typical Therapies for Children With responses. The therapist explains the
development, both fine and gross Developmental and Behavioral child’s behaviors and responses to
motor skills may be delayed in Disorders,” providing important caregivers in sensory terms and
preschool-aged children with ASD.372 background information and provides them with strategies to help
Attention to position in space in recommendations for the caregivers accommodate the
children with a coexisting diagnosis pediatricians.376 Since that child’s sensory needs to decrease
of ADHD may further complicate publication, the DSM-5 criteria now functional impairment and tolerate
delays in coordination.373 includes sensory symptoms in the environmental triggers. Advocates of
Occupational therapy services may diagnostic criteria for ASD in these interventions claim that
be indicated to promote fine motor recognition of the fact that individuals dysfunction in integration of sensory
and adaptive skills, including self- with ASD have sensory challenges input contributes to inefficiencies in
care, toy use, and handwriting. that may be related to repetitive and learning and to behavioral challenges
Almost two-thirds of preschool-aged other challenging behaviors.377 and that therapeutic approaches to
children with ASD are reported to Indeed, sensory symptoms exhibited sensory integration need to be
receive occupational therapy by young children, such as food considered separately from focal
services.374 selectivity, covering their ears for sensory-based treatments.379
certain sounds, and visual scrutiny of Although sensory-based therapies are
Similarly, some children with ASD among the most commonly requested
aspects of objects, may be among the
may have gross motor impairment
earliest differences families identify therapies by caregivers,361 the
on formal testing that may benefit evidence supporting their general use
in their children’s development.
from therapeutic intervention
Sensory goals may be included in remains currently limited.378,379 As
focused on building strength, with any other intervention, specific
treatment objectives for students
coordination, motor planning, or goals for sensory-based therapies
with ASD. Adult-directed approaches
skill acquisition to promote safer should be identified, and outcomes
provided through sensory-based
mobility or play. Toe walking is should be monitored so that the
interventions may be included in the
common among children with ASD utility for any given child can be
context of motor and behavioral
as well as in other developmental
therapies and in educational settings. documented.376
disorders in early childhood. The
Despite the increasing scientific Medical Management of
etiology of toe walking in ASD is
understanding of the neurobiological Co-occurring Conditions
unclear, although sensory aversion
basis for sensory symptoms in
and habit or perseveration have Co-occurring medical and other
individuals with ASD, empirical
been proposed. Common conditions, such as seizures, sleep
interventions in common practice
interventions for toe walking may disorders, gastrointestinal (GI)
have modest evidence to support
include passive stretching, orthotics, disorders, feeding disorders, obesity,
their general use at this time.378
and casting. Impairment in gross catatonia, and others, have
Commonly used sensory-based
motor function may affect the interventions, including brushing of a significant effect on the health and
capacity of a child with ASD to quality of life for children and youth
the skin, proprioceptive stimulation
participate in leisure activities with with ASD and their families.380,381 In
by using weighted vests, or
the family or with peers and may this section, the co-existing conditions
kinesthetic stimulation (such as
impair participation in sports or swinging or use of specialized seating, commonly observed in children and
interactive play beyond the effect of such as a therapy ball, to modulate youth with ASD are described, and
their social skills alone. Impaired level of arousal), are not yet anticipatory guidance and
motor skills may further decrease supported in the peer-reviewed management strategies that primary
opportunities for social skills literature. care providers may consider are
development and active learning and provided.380
may be a risk factor for overweight Proponents of sensory integration
and obesity.375 For motor therapies to therapies distinguish them from Seizures
be provided in the educational interventions with sensory modalities There is both an increased risk for
setting, a significant delay for age that because of the active engagement ASD among children and youth with
affects function in school must be with the child in skill building or epilepsy and an increased risk for
identified on a valid assessment desensitization. This type of therapy seizures in those with ASD. The
measure. requires a trained clinician, often an pooled risk for ASD among children

with epilepsy is 6.3%, with almost were later diagnosed with ASD.388 Feeding Disorders
5 times as many in samples with the Because of language delays and Up to three-quarters of children with
highest rates of co-occurring atypical sensory perception or report ASD have problems related to eating,
intellectual disabilities.173,382,383 The of pain, individuals with ASD may be including food selectivity based on
rate of seizures among people with less likely to report specific GI texture, color, or temperature; rituals
ASD in community-based populations discomfort and may present with around food presentation; and
has been reported to range from 7% agitation, sleep disruption, or other compulsive eating of certain
to 23%, with rates as high as 46% behavioral symptoms rather than GI foods.397–399 Behavioral refusal may
reported in clinically ascertained discomfort.387 Characteristics of ASD also present as the child holding food
samples.170 It has been suggested that might affect GI symptoms include in the mouth, volitional gagging, and
that the risk for seizures is not resistance to change (feeding and emesis. Common related problems
increased in individuals with ASD constipation), comorbid anxiety include pica (eating of nonfood items)
without intellectual disability. Risk (pain, feeding, and motility and rumination (self-stimulatory
factors for the increased likelihood of disorders),389 and altered sensory emesis and reswallowing of stomach
seizures in people with ASD include perception (pain, feeding, and contents). By age 16 months, children
intellectual disability (as noted), constipation). At present, there is no who are later diagnosed with ASD are
female sex, and lower gestational evidence of an association of ASD observed to be more selective in their
age.174 Specific genetic disorders with celiac disease, specific immune eating patterns than are other
associated with ASD, such as tuberous dysfunction, or motility disorders (eg, toddlers.400 Problems around
sclerosis, also may contribute to gastroesophageal reflux) in children mealtime behavior and food choice
seizure risk in early childhood. Onset with ASD. often persist into adolescence. The
is bimodally distributed, with most frequency of feeding challenges in
first seizures occurring in early It would be expected that these children and youth with ASD may
childhood and in adolescence; 20% of disorders would occur at least as relate to the core symptoms of
first seizures occur in adults with frequently among individuals with restrictive and repetitive behavior
ASD.170 Children with ASD and ASD as among individuals in the and differences in sensory perception
seizures tend to have more behavioral general population, and they should related to smell, taste, and texture.401
challenges, independent of cognitive be considered when the child has
skills.382 Screening EEGs are not a history of GI symptoms or a change Children with developmental delays
recommended for patients who are in behavior.390,391 Ongoing research is may also have delayed oral motor
asymptomatic. An overnight EEG focused on whether differences are skill development and may
should be considered when the present in immunologic function, demonstrate food refusal of textures
clinical history suggests seizures and motility, or the microbiome in that they cannot physically chew or
atypical regression. Response to individuals with ASD.392–394 swallow. Discomfort can lead to food
conventional antiepileptic drug refusal, so initial evaluation should
therapy varies greatly, with some Selective eating is common in include consideration of
reports suggesting an increased risk children with ASD.386 A limited diet gastroesophageal reflux, dental pain,
for treatment-resistant epilepsy in may influence GI symptoms, such as food allergies, lactose intolerance, and
individuals with early onset of constipation,395 and alter the significant constipation.387 If oral-
seizures and delayed global intestinal microbiota. GI disorders motor concerns are observed, speech
development.384 should be considered in patients with or occupational therapy assessment is
ASD if they present with typical GI indicated.
GI Symptoms symptoms or with agitation, food
GI symptoms, such as abdominal pain, refusal, or sleep disturbance.387,396 Because feeding problems are so
constipation, diarrhea, The indicated GI workup will depend common among children with ASD,
gastroesophageal reflux, and feeding on the specific symptoms. Children a dietary history should be obtained
problems, are more commonly with ASD should be offered the same at health supervision visits.
reported in children and adolescents approaches to treatment of GI Physiologic needs for macronutrients
with ASD than in those with disorders as other children. and micronutrients are the same for
developmental delay or typical Modifications of conventional children with ASD as for other
development.385–387 A large interventions to accommodate for children. As with other children in the
prospective cohort study revealed symptoms of ASD might include United States, insufficient intake of
differences as early as 6 to 18 months consistent behaviorally informed fiber, vitamin D, and calcium are
of age in stooling patterns and approaches for constipation and common.402 Rare cases of severe
feeding behaviors in children who encopresis. nutritional deficiencies, such as

rickets (vitamin D),403 scurvy eating patterns that may include persistence of pica in children and
(vitamin C),404 and keratoconus energy-dense foods, and are more youth with ASD because of the risk
(vitamin A),405 have been reported in likely to be prescribed medications, for toxic ingestions, risk for lead
children with ASD with severe food such as atypical neuroleptics (or intoxication, potential for infection,
aversions. If supplements are used to antipsychotic medication) and and the risk for mechanical ingestions
correct for poor vitamin D or calcium anticonvulsants, that often contribute ranging from batteries to bezoars.418
intake, it is important to confirm that to excessive weight gain. Sleep Obstruction and perforation need to
the dose is sufficient for the age and disorders may further predispose be considered in children with pica
sex of the child.406 Food fortification them for obesity. Primary care who have acute abdominal
in the United States may supply providers should monitor a child’s symptoms. Iron deficiency is
adequate amounts of vitamins and age-specific BMI percentile in the associated with pica in the general
minerals for some children with context of health supervision care and population.419 Laboratory monitoring
selective diets, so additional address modifiable risk factors of blood lead and iron deficiency in
multivitamins may not be through anticipatory guidance for children with pica is suggested in the
necessary.407 Consultation with their patients with ASD. Programs context of primary care. Behavioral
a registered dietitian may be helpful that address healthy weight for intervention includes reinforcing
to be able to guide families regarding children and youth with typical appropriate behaviors, ensuring adult
the nutritional sufficiency of their development may need to be supervision, and putting into place
child’s diet. modified for successful use for environmental safeguards for
patients with ASD.414 prevention.
The clinician can counsel families
about offering children routine meals Dental Health Sleep Problems
and snacks, discouraging snacking
Children with ASD commonly have Sleep disturbance is common in
through the day, promoting self-
unmet dental needs. Difficulty individuals with ASD and may be
feeding, and using basic behavioral
cooperating with hygiene and associated with exacerbation of
approaches to encourage mealtime
professional care are reported problematic daytime behavior.420–427
structure and predictability with
barriers for dental care. Even when Problems with initiating and
minimal distraction. Children with
insurance coverage is available, maintaining sleep are reported for
ASD need to be offered new foods
children with ASD have fewer visits 50% to 80% of children with ASD.428
multiple times to become familiar
for routine care.415 There are limited Children who are later diagnosed
with them. Feeding problems that
data about the prevalence of caries or with ASD are reported to have had
affect nutrition or family function or
gingival disease in children with ASD. sleep problems by 30 months of
that are specialized, such as mouth
As with other children, anticipatory age.429 Sleep problems in individuals
packing, rumination, severe pica, and
guidance should include attention to with ASD persist; almost half of
intense aversions, are likely to need
dental hygiene and fluoride use, if adolescents with ASD continue to
the support of professionals with
appropriate, from a young age. have sleep symptoms.430 Adolescents
expertise in behavior management
Behavioral strategies may be helpful are more likely to have shorter sleep
and/or oral-motor therapies (speech
to prevent the need for dental care duration, daytime sleepiness, and
or occupational therapy).408,409 Food
under sedation. delayed sleep onset compared with
refusal may stem from discomfort, so
younger children with ASD, who are
consultation with a gastroenterologist Pica more likely to have bedtime
may be helpful. Gastrostomy-tube
Children and youth with ASD may put resistance, parasomnias, and night-
placement and nonoral feeding
nonfood items in their mouths long waking. Reasons for the increased
should only be considered after
after the developmental period of frequency of sleep disturbances in
appropriate behavioral intervention
early childhood, when pica is children and youth with ASD may
has failed.
expected. Pica is reported in up to include differences in melatonin
one-quarter of preschool-aged metabolism,431 developmental
Obesity children with ASD and is documented disruption of other neurotransmitter
Children and youth with ASD have to persist in individuals with systems critical to sleep, and lack of
greater risk for overweight and intellectual disability.416,417 The social expectations, among other
obesity than those in the general persistence of pica may be explanations. Genetic disorders, such
population.410–413 People with ASD attributable to sensory differences, as Smith-Magenis syndrome, are
have fewer opportunities and perseveration or obsession, and oral associated with both ASD and sleep
perhaps less interest for active leisure exploration of the environment. disruption.432 Biological reasons for
or organized sports, have repetitive Clinicians need to be aware of disrupted sleep that are not unique to

children with ASD may include challenges, behavioral strategies are were at risk for traffic-related injury
restless leg syndrome, which may be successful when consistently and almost one-third were reported
associated with low iron stores,433 implemented.440 to have had near-drowning episodes.
and coexisting neurologic or Data from a national survey revealed
No medication is currently approved
behavioral diagnoses, such as that elopement attempts in the past
by the US Food and Drug
epilepsy, anxiety, ADHD, or mood year were reported by approximately
Administration for the treatment of
disorders. The most common cause one-third of parents whose children
insomnia in children with or without
of both delayed sleep onset and night had ASD with or without intellectual
ASD. Any medication elected should
wakings are learned behaviors. As disability.449 Wandering may persist
be started at a low dose and
with other children, the evaluation of into adulthood.
monitored for adverse effects.427
the child with ASD with delayed
Sleep onset may be aided by In the survey by Anderson et al,447
sleep onset, night wakings, and/or
treatment with melatonin441,442 at parents reported that the most
early-morning wakings should
doses from 1 to 6 mg443 and may be common perceived reasons for
include a history of comorbid
maintained with long-acting elopement were enjoyment of
medical conditions that might
melatonin.442 Adverse effects are running, attempts to get to a desired
disrupt sleep, such as
uncommon but may include location (such as a park), pursuit of
gastroesophageal reflux, seizures,
nightmares. a-adrenergic agents (eg, an intense interest (eg, water), and
asthma, allergies, eczema, or
clonidine) and antihistamines (eg, escape from situations or sensory
enuresis. Snoring might suggest
diphenhydramine) are often events that made them anxious.
obstructive sleep apnea and would
prescribed to help with sleep onset or Because the risk for elopement
prompt referral for additional
to address night-waking in children, increases with the severity of ASD
assessment. Children who play video
but the literature provides little and with co-occurring intellectual
games or engage in other screen time
support for their use.444,445 disabilities, many of the individuals at
close to bedtime have later bedtimes
Disordered sleep is associated with greatest risk have limited language
and may have more difficulty falling
challenging daytime behaviors in and cannot tell first responders their
asleep.434,435 Restless sleep and
children with ASD446; addressing one names, addresses, or phone numbers
night wakings would suggest a need
may help with the other. if they get lost. Police may interpret
for laboratory evaluation for ferritin
aggression caused by fear as
and other indicators of iron
Wandering combative behavior.
sufficiency to determine if low iron
stores might be present.428 An Accidents, including drowning, are Prevention is the most important
environmental history of the a major cause of morbidity and intervention for elopement. Parents
household may help to determine if mortality in children and youth with participating in a large national
household noise, parental work developmental disabilities, including survey of children with special health
hours, or other factors may affect ASD.447,448 Children and youth with care needs reported primarily using
sleep. The bedtime routine and ASD may have decreased awareness physical and electronic barriers to try
response to night-waking should be of social convention and community to prevent elopement, especially in
reviewed to determine the rules as well as impulsivity and children who also had intellectual
behavioral approaches to consider. perseverative interests that draw disabilities.447,449 Information on
them to potential dangers, such as prevention and management of
Empirical support exists for the bodies of water and busy roads. wandering is available for parents
effectiveness of parent education and Wandering off (also called and clinicians (http://
behavioral interventions for children elopement) places them at risk for nationalautismassociation.org/big-
with ASD and sleep injury. Wandering, if present, should red-safety-box/). Consistent,
disturbances.425,436–440 Behavioral be included in the problem list as adequate adult supervision is
intervention includes parents a coexisting diagnosis in patients with important in all environments: school,
establishing bedtime routines and ASD. In an online study, 1218 families home, and community settings.
making clear their expectation that of children with ASD were questioned Families note that increased
the child sleeps in his or her own bed. about elopement.447 Nearly half of supervision needs result in increased
This may be difficult to establish for children with ASD between the ages family stress. Families may need to
children with ASD, who may not of 4 and 10 years had tried to elope. consider deadbolts, fencing, and
appreciate the social conventions Almost half of those children were alarm systems for safety as well as
around sleep time and may have missing long enough for their parents personal GPS devices and
repetitive rituals and comorbid to contact the police. Of those identification bracelets or other
anxiety or ADHD. Despite these children, approximately two-thirds identification. Local law enforcement

agencies may support GPS tracking. literature base.451 Later loss of motor home and school functioning is often
Alerting neighbors and local law skills in adolescence should prompt assessed as part of school testing by
enforcement officials as well as evaluation by a neurologist for using parent and teacher
securing pools in the neighborhood underlying reasons. Regression in questionnaires, such as the Behavior
and creating a family emergency plan language or social interest is reported Assessment System for Children,
are suggested. If impulsivity and in approximately one-quarter of Third Edition, Parent Rating
motor hyperactivity contribute to children later diagnosed with ASD. It Scales,79,462 or the Child Behavior
elopement, examining the utility of is recognized most commonly Checklist.82,463,464
medication as part of an overall plan between 18 and 24 months of age.
With change in behavioral symptoms,
may be considered. Similarly, Regression later in childhood
physical sources of discomfort and
addressing sleep issues becomes requires evaluation.
behavioral intervention should be
important if the child is at risk for
Co-occurring Behavioral Health considered.465 If behavioral
wandering at night. Teaching safety
Conditions interventions are insufficient to
skills and appropriate community
address the challenges or are
behaviors is critical to prevention. All Co-occurring behavioral symptoms
unavailable at the time, medication
children with ASD, no matter their include hyperactivity or inattention,
might be considered (see Table 10 for
level of cognitive skills, are at risk for aggression, outbursts, and self-
guidance on prescribing medication).
wandering.449 injurious behaviors. Although these
behaviors are not core features of
ASD, they commonly interfere with ADHD
Motor Disorders
functioning in school, at home, and in Changes in DSM-5 criteria have
There is increasing appreciation that
the community and contribute provided flexibility to diagnose other
individuals with ASD may have
substantially to the challenges faced DSM-5 disorders in addition to ASD,
developmental coordination disorder
by families.293,294,381,452–457 which can help guide treatment.
and other neurologic problems. Tic
Psychiatric conditions (such as ADHD, Approximately half of children and
disorders occur with an increased
anxiety, OCD, mood disorders, youth with ASD also may fulfill
frequency in children with ASD.450
conduct disorders, or others) are diagnostic criteria for ADHD.459
Distinguishing complex tics from
identified in 70% to 90% of children Pediatricians should keep in mind
stereotyped movements may be
and youth with ASD.458,459 Behavioral that some children who are later
challenging.
challenges have a significant effect on diagnosed with ASD may have been
Catatonia was added as a possible health and quality of life for children initially identified as having ADHD.69
coexisting condition to ASD in the and adolescents with ASD and their Symptoms of ADHD may further
DSM-5. Slow initiation of movement families.460 Patients with ASD, like compromise social skills function in
and reported deterioration in motor other children and adolescents, children with ASD because of
performance have been treated with should be regularly screened for inattention to social cues and
lorazepam, electroconvulsive therapy, behavioral and/or emotional impulsivity. Standard rating scales
and behavioral interventions, but the conditions, as recommended by the used to assess symptoms of ADHD
therapies do not have a strong AAP.461 The effect of behavior on have not yet been validated for
TABLE 10 Considerations Surrounding Medication Use

No current medication corrects core social and communication symptoms of ASD
Accurate diagnosis of coexisting psychiatric conditions guide therapy
Medication is used to help manage
• Coexisting behavioral health disorders (eg, ADHD, mood disorders, or anxiety disorders)
• Associated problem behaviors or symptoms causing significant impairment and distress
o Examples include the following: aggression, self-injurious behavior, sleep disturbance, mood lability, anxiety, hyperactivity, impulsivity, inattention
Medication should only be considered after
• Careful accounting of when the behavior started and what seems to exacerbate it
• A functional behavioral assessment should guide development of a treatment plan in the school setting
o Consider whether the behavior serves as communication of distress or refusal
• Consider referral to a behavior therapist outside of school to assess the reasons for the behavior, provide the family with strategies, and collaborate in
care
• Careful history and physical to look for medical factors that may cause or exacerbate challenging behaviors (eg, gastroesophageal reflux and acute
sources of pain, such as otitis media, dental injury, fracture, and others)34,380,391,485,579
Consider medication after treatable medical conditions and behavioral factors assessed and intervention does not address the symptoms of concern
Include the family and patient in shared decision making that considers their goals and values543

individuals with ASD. However, they and generalized anxiety disorder as if anxiety is exacerbated by
are useful in determining the clinical well as unspecified anxiety disorder. uncertainty or associated with
impact of symptoms for an individual As many as 40% to 66% of school- sensory under- and overreactivity.377
patient and in monitoring treatment. aged children and adults with ASD Nonpharmacologic approaches, such
It is important, however, to consider are reported to also have anxiety as neurofeedback and digitally
the differential diagnosis of disorders.458,459 Anxiety disorders delivered approaches to self-
inattention and hyperactivity in the are most commonly identified in regulation, are being evaluated for
context of the language impairment children with ASD and typical their therapeutic potential.
and perseverative focus that often cognitive and language abilities.468,469 Medications used for anxiety in the
accompanies ASD. Children with Symptoms may be present in early general population may be
delayed language may appear more childhood and manifest as behavioral considered as part of an overall
inattentive. If they are expected to challenges, such as overreactivity. treatment plan for children and youth
perform activities (including Biological predisposition to both ASD with ASD (see Table 11 for
schoolwork) that they are not able to and anxiety may be attributable to psychopharmacotherapy of children
understand or accomplish, a child common genetic factors and/or with ASD and anxiety).
with ASD may engage in behaviors to altered neurophysiologic responses to
escape, which can be interpreted as stress.470 Mood Disorders
inattention and hyperactivity. Patients Depressive disorders are more
Core symptoms of ASD decrease the
with ASD may be focused on their common among children and adults
ability of individuals with ASD to
perseverative interests and may be with ASD than in the general
predict the actions or interpret the
internally distracted, as opposed to population. Reported rates of
beliefs of others, which may lead to
distracted by the environment. coexisting depression in adults and
a constant state of heightened worry.
Evaluation of the symptom of children are highly variable, ranging
Repetitive behaviors may, in part,
inattention or impulsivity includes from 12% to 33%.458,476,477
serve to instill predictability, so
assessing language and educational Symptoms of depression are more
anxiety may lead to increased
abilities. Appropriate educational likely to lead to dual mental health
stereotyped behaviors or
modifications and use of language for and developmental disability
perseverative thoughts. Evaluation of
instruction that the student can diagnoses in adolescents and adults
anxiety requires consideration of the
understand are critical for successful with ASD than in children. The
language demands of the
intervention. Behavioral strategies coexistence of mood disorders and
environment, academic expectations,
should address reinforcement of on- ASD may be associated with genetic
social demands, and underlying fears
task behaviors, breaking down tasks and neurobiological factors as well as
or phobias. Youth with ASD may lack
into units that can be completed environmental factors related to
sufficient language or insight to
successfully, breaks for activity (often chronic stress and difficulty with
describe their symptoms. Getting
included in sensory activities), and understanding social situations. Both
information from multiple sources
adult supervision appropriate for the elevated and depressed mood may
and looking at the behavioral
demands. The same medications that present as behavioral symptoms in
manifestations related to context will
are used for symptoms of ADHD in youth with ASD. Changes in affect,
help to correctly identify anxiety in
children without ASD are used in participation, sleep habits, and eating
patients with ASD.471
similar doses for children with may be symptoms of an underlying
ASD.466 Routine monitoring is Strong evidence from RCTs supports mood disorder. Attempted suicide is
important because children with ASD the use of cognitive behavioral reported to occur more frequently in
may be at greater risk for adverse therapy for anxiety symptoms in people with ASD than in the general
effects467 (Table 11). The evaluation school-aged children with ASD, population. Risk factors include peer
of a child for a possible co-occurring especially those with typical-range victimization, behavioral problems,
diagnosis of ADHD also should intelligence.295,298,472–475 Anxiety minority race or ethnicity, male sex,
include consideration of a co- may be associated with reported GI lower socioeconomic status, and
occurring diagnosis of anxiety.464,466 and sensory symptoms.389 Some lower level of education.478 The AAP
individuals find that sensory recommends screening for
Anxiety Disorders redirection or sensory activities used depression in patients older than
The DSM-5 classification system in the context of a behavioral 12 years. Until ASD-specific measures
separates anxiety disorders into program are helpful to diminish are developed, the same approaches
separation anxiety disorder, selective feelings of anxiety. Other individuals used for all other adolescents at
mutism, specific phobia, social may find symptom relief with the increased risk for depression should
phobia, panic disorder, agoraphobia, introduction of routine and structure be considered.479

TABLE 11 Psychotropic Medication Options for Common Target Symptoms
Target Symptoms Medication Class (Examples) Comments
Hyperactivity Psychostimulants (methylphenidate, dexmethylphenidate, With other coexisting symptoms, medication may not appear
Impulsivity mixed amphetamine salts, lisdexamfetamine, as effective
Inattention dextroamphetamine)466,580–587 May be more sensitive to adverse effects
Distractibility SNRIs (atomoxetine)588–590 Steps:
a-2 adrenergic agonists (clonidine, guanfacine)591–594 • Behavioral approaches implemented
Atypical (second generation) antipsychotics (aripiprazole, • Problems persist, trial of medication management
risperidone)595–598 • Start with a low-dose stimulant (eg, methylphenidate or
mixed dextroamphetamine salts) and increase as needed
and tolerated
May be most effective in children without comorbid
intellectual disability
Targets symptoms of impulsivity and hyperactivity
• If there are adverse effects or if not effective:
Consider atomoxetine, especially if also with social anxiety
Consider a-2 agonists (eg, short- or long-acting guanfacine,
clonidine)
Other medications (less evidence): atypical antipsychotic
medications may decrease hyperactivity; their primary
use is for irritability and aggression
Adverse effects:
Psychostimulants: appetite suppression and insomnia; also
irritability, depressive symptoms, and social withdrawal;
it does not appear to worsen repetitive behavior or
oppositional behavior
Guanfacine, clonidine: drowsiness, fatigue and irritability;
may also include appetite suppression, nausea, sleep
disturbance, and decreased blood pressure and heart
rate; rebound if not weaned
Irritability and severe disruptive Atypical (second generation) antipsychotics (aripiprazole, Medication most effective if combined with behavioral
behavior risperidone)595–608 strategies addressing identified environmental causes for
• Vocal and motoric outbursts of the behavior and developing more appropriate responses
anger, frustration, and distress for the child
• Acts of aggression, self-injury, DB/PCs strong support for 2 second-generation atypical
property destruction antipsychotic medications (risperidone and aripiprazole)
• Behaviors referred to by for reducing irritability, stereotyped or repetitive
caregivers as “agitation,” movements, self-injury, and hyperactivity
“tantrums,” “meltdowns,” or • Risperidone and aripiprazole are currently the only
“rages” medications with FDA-approved labeling specific to
irritability in ASD
Adverse effects and monitoring:
• Common adverse effects include wt gain and dyslipidemia
• Monitoring: periodic assessment for extrapyramidal
symptoms; measurement of wt, height, and BMI; and
laboratory monitoring of glucose and lipid levels
• Metformin might be a useful treatment to help control wt
gain.609
Other agents in this class, such as olanzapine and quetiapine,
may have utility on the basis of their adverse effect profiles
but do not have current FDA package insert indication for
use in children with ASD
a-2 adrenergic agonists (clonidine, guanfacine)591,610 Small studies documenting beneficial effects on irritability;
need larger trials; may have better adverse effect profiles
than atypical antipsychotics
SSRIs (fluvoxamine, citalopram)611,612 Few studies focused on irritability and/or aggression; some
reporting improvement in irritability; insufficient evidence
to advise practice

TABLE 11 Continued
Target Symptoms Medication Class (Examples) Comments
Anticonvulsant mood stabilizers (valproic acid and Small studies suggestive of improvement in irritability; need
divalproex sodium)613–618 larger studies; a limited number of placebo-controlled
studies either do not support or are inconclusive regarding
anticonvulsant medication as a treatment of irritability in
patients with ASD
Serotonin-norepinephrine reuptake inhibitor Effect size of improvement associated with venlafaxine was
(venlafaxine)619 small, and irritability was not the primary outcome
measured
Repetitive behavior Atypical (second generation) antipsychotics (aripiprazole, Multiple DB/PCs documenting improvement in repetitive
• Stereotyped motor mannerisms risperidone)595–598,620 behavior; short-term treatment
• Compulsions Common adverse effects include increased appetite, fatigue,
• Behavioral rigidity, insistence on drowsiness, dizziness, and drooling
sameness More effective for targets of tantrums, aggression, and SIB
Anticonvulsants (valproic acid and divalproex Modest improvement has been reported with divalproex
sodium)613,621,622 sodium treatment
May have improvement with topiramate as a second agent
with risperidone
Most antiseizure drugs have potential for sedation, cognitive
adverse events
SSRI (fluoxetine, fluvoxamine)480,509,611,612,623–627 Studies to date have not revealed effectiveness of SSRI
medications for repetitive behaviors related to ASD,
although they may diminish anxiety
SSRIs may be effective for reducing symptoms of OCD and of
anxiety when included in a comprehensive approach to
treatment
Need comprehensive behavioral approaches to minimize
repetitive behaviors
Anxiety, depression SSRIs469,628 Anxiety relief has been reported in trials of citalopram and
buspirone, with fluvoxamine revealing some effect in
female patients with ASD; documented utility in children
and youth without ASD
a-adrenergic (clonidine, guanfacine) Hyperactivation is an adverse effect of SSRIs in children and
youth with ASD that may result in stopping the medication
The anxiety disorders most amenable to treatment are
generalized anxiety disorder, separation anxiety disorder,
and social phobias
Atypical (second generation) antipsychotics469,620 If a mood dysregulation disorder is identified, treatment with
a mood stabilizer and/or a second-generation antipsychotic
is recommended, although an SSRI may be used to treat
comorbid anxiety, OCD, or depression; behavioral activation
with hypomanic or manic switches has been reported
First-line treatment is a program of cognitive behavioral
therapy to reduce symptoms472–475
Few studies have examined the specific effects for these
symptoms; clinicians may consider use of these agents;
although SSRIs, SNRIs, and/or buspirone may be effective
for the treatment of anxiety in children with ASD, they have
not been rigorously evaluated for this
purpose507,626,627,629,630
Medications to consider include sertraline, fluoxetine,
citalopram, or escitalopram for symptoms of anxiety and
a-2 agonists (eg, guanfacine and clonidine and b-blockers
such as propranolol), which may be useful for anxiety-
related physiologic symptoms and behavioral
dysregulation, and a short-acting benzodiazepine, such as
lorazepam, could be considered for event related anxiety
DB/PC, double-blind placebo-controlled trial; FDA, US Food and Drug Administration; SIB, self-injurious behavior; SNRI, selective norepinephrine reuptake inhibitor. Adapted from Riddle MA.
Pediatric Psychopharmacology for Primary Care. 1st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2016.

As in children and youth with typical performed to reduce anxiety. Unlike Table 11 for medication
development, assessment of the stereotypic behaviors of ASD, management).
depression and other mood disorders compulsions usually follow an
must include family history, history of obsession, diminish anxiety, and are Disruptive Behavior Disorders:
environmental stressors, the potential not desired by the individual or Aggression, Self-Injurious Behavior, and
for toxic ingestions, and evaluation perceived as pleasurable.482 Under Tantrums
for comorbid conditions. the DSM-5, OCD-related disorders Disruptive behaviors, such as
Interventions for depression include include hoarding disorder, excoriation aggression, self-injury, and tantrums,
supportive therapy, cognitive (skin-picking) disorder, may complicate home and community
behavioral therapy, and medication, if trichotillomania, substance- or management of individuals with ASD.
indicated, as coordinated medication-induced obsessive- Behavioral outbursts may occur in
interventions (see Table 11 for compulsive and related disorder, and response to stressful events in the
medication use). Antidepressant use obsessive-compulsive and related environment, in reaction to a medical
in people with ASD has not been disorder due to another medical condition, as functional
demonstrated to address aggression condition. The perseverations communication, or as a symptom
and has inconsistent effect on associated with ASD may be supporting diagnosis of a co-
anxiety.480 Medication qualitatively different and less occurring mental health disorder.485
recommendations are based on data sophisticated than the repetitive and Functional behavioral analysis and
from the general pediatric population intrusive thoughts and actions implementation of behavioral
and expert consensus.469 associated with OCD.483 Repetitive strategies can be an important initial
behaviors in general may help an step in management.486 A proposed
The DSM-5 criteria for bipolar illness
individual with ASD regain a sense of pathway for the primary care setting
include changes in activity, energy,
predictability. Anxiety, phobias, and/ for management of irritability that
and mood. It may be difficult to make
or depression may coexist with OCD leads to disruptive behaviors in youth
a diagnosis in people with ASD with
in youth with ASD. with ASD is proposed by McGuire
limited language. The co-occurrence
et al.485 Disruptive behaviors may
of bipolar illness and ASD in Behavioral approaches are serve as communication to escape
individuals with typical intelligence recommended as the first line of from a demand or an undesired
ranges from 6% to 21%.481 Lifetime treatment of symptoms of OCD, situation. If successful, they may
diagnosis of bipolar illness in adults depending on the language and become part of a behavioral pattern.
with ASD is reported to be 9%.458 cognitive level of the patient. New onset of severe behaviors
Cognitive behavioral therapy, requires consideration of potential
OCD-Related Disorders including exposure and response medical reasons (see Table 12).
Although restricted and repetitive prevention with or without a selective Pharmacologic treatment should be
behaviors are symptoms of ASD, serotonin reuptake inhibiter, has considered if no medical etiology is
some individuals with ASD may also been demonstrated to be the most identified and if the behavior is
have coexisting OCD. Obsessions are effective treatment for youth with associated with irritability, is not
recurrent, unwanted, and persistent OCD who do not have ASD. Cognitive responsive to available behavioral
thoughts, images, or urges that cause behavioral therapy may be less interventions, or is related to a co-
distress. Compulsions are repetitive effective, with fewer remissions, in occurring diagnosable behavioral
behaviors or thoughts with rigid rules youth who also have ASD484 (see health disorder, such as anxiety, mood
TABLE 12 Common Presentations of Self-Injurious Behavior and the Medical Conditions to Consider If New Onset
Type of Self-Injury Potential Associated Conditions Potential Associated Injury
Head banging Headache, toothache, sinus infection, ear infection Detached retina, abrasions, contusions
Head hitting or slapping Headache, toothache, sinus infection, ear infection Fracture of bones in hand, detached retina, abrasions, contusions
Eye poking Vision loss, eye pain Eye abrasion
Gum or tooth digging or Dental pain, gingivitis Gum injury, tooth autoextraction, tooth fracture
banging
Scratching and skin Allergy, eczema, drug reaction, skin infection or Infection, scarring
picking infestation (eg, fleas, scabies)
Finger and toenail biting Pain Infection, nail removal, ingrown nails, paronychia
or picking
Kicking or stomping Restless leg syndrome, leg pain Bruises, fractures
Rumination Gastroesophageal reflux, eosinophilic esophagitis Esophageal ulceration and bleeding, dental damage, nutritional
compromise, precancerous lesions of esophagus

disorders, thought disorders, and/ hyperactivity, impulsivity, repetitive behavior or coexisting psychiatric
or ADHD. behavior, and more challenges with diagnoses.476,497–501 Prescription of
social interaction.491 There is an medication also appears to be
It has been reported that between 8%
association of self-injury with specific affected by demographic factors, such
and 68% of children with ASD
genetic disorders that are not as race, ethnicity, and
demonstrate aggressive behavior,
associated with ASD, such as the geography.497,498,502 Reported
depending on how stringent the
severe self-biting of Lesch-Nyhan polypharmacy rates range from 12%
definition is.454 Aggressive behaviors
syndrome. Self-injurious behavior is in a registry cohort recruited from
were reported on the Child Behavior
associated with genetic disorders that diagnostic clinics499 to 29% to 35%
Checklist for one-quarter of children
are also associated with ASD, such as in large studies of Medicaid claims
attending an ASD clinic, with similar
Cornelia de Lange syndrome, fragile X data.476,493
rates from 2 to 16 years of age.
syndrome, and Smith-Magenis
Aggression was associated with Medication may be helpful to address
syndrome.492 In the case of
hyperactivity, lower cognitive skills, co-occurring symptoms or disorders.
aggressive, self-injurious, and
sleep problems, and internalizing Clinicians should carefully weigh
disruptive behaviors, the primary
behaviors such as anxiety. There was potential risks and benefits before
care provider needs to assess the
no association with sex. Researchers prescribing medication for behavior
safety of the child and family in an
of other studies have observed and use psychotropic medications as
ongoing fashion. Referral to
increased rates of physical aggression part of a comprehensive treatment
community services and for
in children with ASD who have lower approach. The prescribing clinician
behavioral intervention should take
adaptive skills and frequent repetitive should understand the indications
place if behaviors are unsafe or if the
behavior.487 Management of co- and contraindications, dosing,
patient is not responding to the
occurring sleep problems and potential adverse effects, drug-drug
treatment plan.
hyperactivity may be helpful in interactions, and monitoring
a treatment plan488 that includes Psychopharmacologic Approaches to requirements of the medications they
behavioral intervention to address Management prescribe.6 Table 10 provides
aggression and targeted guidance for principles of prescribing
The use of medications to treat
pharmacotherapy.487 medication, and Table 11 lists
behavioral and psychiatric symptoms
Self-injurious behaviors are reported in children and youth with ASD has pharmaceutical options for common
in 40% to 50% of individuals with increased significantly since the behavioral-symptom clusters. Psycho-
ASD at some point across the publication of the 2007 AAP clinical pharmacogenomic testing for genetic
lifespan489 and may occur more reports.493,494 With a shortage of variants that increase the likelihood
frequently in people with ASD who specialists, more medication of adverse effects is an emerging area
also have aggressive behaviors and management, including prescription for precision medicine. Prescribers
sleep problems.490 Self-injurious of atypical antipsychotic medications, should consider CYP2D6 and
behaviors in individuals with ASD is taking place in the primary care CYP2C19 metabolizer status in
may be repetitive and self- setting.495,496 Large national studies making medication decisions for
stimulatory (such as scratching, pica, of insurance claim data from selective serotonin reuptake
or rumination). Head banging and Medicaid and commercial insurers inhibitors (SSRIs), for example,
self-hitting may occur as part of reveal rates of psychopharmacology despite limited data at present to
a tantrum. Like aggression and other prescription for patients with ASD to guide practice.503,504 The limited data
disruptive behaviors, self-injurious be 56% to 65%.476,493,497 One or on the utility of psycho-
behaviors may serve as more psychotropic medications are pharmacogenomic testing at the time
communication to escape from prescribed for 1% of children with of this publication limits insurance
demands or situations that the ASD younger than 3 years, for 10% to coverage for many patients.
individual does not want to be in. The 11% of children aged 3 to 5 years, for Recommendations for testing are
type of self-injurious behavior may 38% to 46% of children aged 6 to expected to rapidly change with
change if the intervention of 11 years, and for 64% to 67% of ongoing research.503–505
prevention or blocking is not adolescents aged 12 to
associated with addressing the 17 years.498,499 Psychotropic Areas of Psychopharmacologic
underlying reason for the behavior. medication use increases with Research
Persistence of self-injurious increased age, lower range of As the neurobiology of ASDs are
behaviors in individuals with ASD is cognitive skills and/or presence of better understood, novel
associated with more limited intellectual disability, and higher psychopharmacologic agents might
cognitive and language abilities, prevalence levels of challenging be developed that will better manage

co-occurring symptoms and/or the past decade, an increasing disease.523,524 The double-blind
address core deficits. Some number of interventions based on clinical trials to date have not
potentially important lines of theories of causation of ASD that are, demonstrated a treatment effect with
research involve medications that as yet, unproven have been examined diet.524,525 Whether a subgroup of
modulate metabolism of excitatory in clinical trials. Appropriately children with GI symptoms might
neurotransmitters (such as glutamate designed trials have provided benefit from these or other dietary
and g-aminobutiric acid), block evidence to support some interventions requires additional
acetylcholinesterase and/or nicotinic interventions, such as the dietary study. Children may be adequately
acid receptors, and act as hormones supplement melatonin, and have nourished on a casein-free diet with
that naturally promote social disproven others, such as secretin.518 calcium and vitamin D
affiliation (such as oxytocin and Many interventions, although still supplementation. Nutritional
vasopressin). Drug trials involve widely used, remain unproven. counseling is recommended if a trial
newly formulated agents as well as of this diet is elected.406 It may be
repurposing exiting medications used Complementary therapies are often that improvement in unrelated
for other purposes.506–509 attractive to families because they are conditions may influence behavioral
purported to correct putative symptoms (eg, removal of dairy
Better understanding of the biological causes of behavioral products may decrease irritability
neurobiology responsible for the symptoms and may be discussed with attributable to lactose intolerance).
symptoms of ASD will allow for the an optimism about outcome that is
identification of targeted often not conveyed with the Dietary supplements are often given
psychopharmacologic interventions. recommendation for conventional to children who are selective eaters
The use of psycho- therapies. Between 28% and 74% of by their families to compensate for
pharmacogenomics to identify which children with ASD are given at least 1, a limited diet.406 However, many
patients might genetically be at and usually more than 1, children with ASD are given vitamins
greater likelihood of benefit or at complementary therapy.519–521 and minerals to treat proposed
increased risk for adverse effects Although use of novel therapies is biochemical abnormalities that have
from specific medications is an common among children with a range been proposed to be unique to ASD.
important area of research.510 of developmental disabilities, children Popular dietary supplements include
with ASD who are irritable or vitamin D,526,527 vitamin B12,528
Integrative, Complementary, and overactive or who are reported to vitamin B6 with magnesium,529
Alternative Therapies have food allergies may be more omega-3 fatty acids,530 and
Despite the advances in likely to be given additional multivitamin preparations. The
understanding the neurobiology of therapies.522 literature to date is controversial with
ASD, many unanswered questions Complementary, alternative, and respect to vitamin supplementation
remain about why ASD occurs and integrative therapies used for ASD as a treatment of symptoms of ASD,
how best to treat it. Families often can be grouped into 3 general areas: and at this time, no conclusive
consider nutritional interventions (1) natural products (including herbs, evidence exists that people with ASD
and nonmedical therapies without vitamins and minerals, and require different nutrient intake than
a scientific evidence base to address probiotics), (2) mind and body that recommended in the Dietary
the symptoms that conventional practices (including yoga, Reference Intakes (https://www.ncbi.
interventions cannot rapidly address, chiropractic, massage, acupuncture, nlm.nih.gov/books/NBK225472/).
or there is limited access to progressive relaxation, and guided The long-term risks of high-dose
conventional services in their imagery), and (3) other therapies supplementation have not been
community. Primary care providers (including traditional medicine and studied.531 Although maternal folic
are often asked about nonstandard naturopathy).517 acid status may provide biologically
interventions that are used in plausible risk for ASD, there is no
integrative practice or are promoted Dietary interventions used to treat evidence that supplementing with B
on the Internet, in the popular press, symptoms of ASD are perceived by vitamins has therapeutic benefit at
by other families, and by many families as beneficial because this time, whether a child carries
celebrities.511–516 The National they are natural and without adverse common variants in the MTHFR
Center for Complementary and effects. Dietary elimination of gluten- gene.532,533 Of dietary supplements in
Integrative Health maintains a Web and casein-containing foods is often common use, melatonin has been
site in which current information on implemented in an attempt to demonstrated to be a safe and
novel therapies in popular use for ameliorate core symptoms of ASD, effective intervention for sleep in
people with ASD is reviewed.517 In not on the basis of allergy or celiac children with ASD.428

Nonbiological interventions used for and national agenda for ASD has with special health care needs (such
symptoms of ASD are popular and emerged and has shaped approaches as Family Voices and Parent2Parent),
have also been increasingly studied. to community services as well as autism-specific national support
There has been conflicting evidence research planning.543 Provision of organizations (such as Autism Speaks
regarding the effect of music patient- and family-centered care and the Autism Society), and local
therapy,534 yoga,535,536 massage,537 requires the clinician to educate the organizations are effective in helping
and equine-assisted therapy538,539 on family about the child’s health and families obtain information and feel
the symptoms of ASD in children, but engage in respectful dialogue. supported. Clinicians should
evidence does not support these Resources to support the clinician in familiarize themselves with national
therapies for treatment of the core talking to families about the diagnosis and local sources of support and
deficits of ASD at this time. Evidence include a toolkit developed by the information so that families can be
to date does not support the use of Autism Speaks Autism Treatment given Web sites or phone numbers at
auditory integration training, in Network (https://www. the time of diagnosis and again as
which an individual listens to altered autismspeaks.org/tool-kit/atnair-p- indicated. State-specific information
sounds through headphones in an guide-providing-feedback-families- on services and Maternal and Child
effort to change auditory or other affected-autism). Health Bureau–supported programs
processing.540 Existing studies are are found online (https://mchb.hrsa.
insufficient at this time to support Impact of ASD on the Family gov/maternal-child-health-
dance therapy, drama therapy, and The impact of having a child with ASD initiatives/autism). It is important
chiropractic therapy.541 on other family members and on for providers to advocate for
society is considerable. Parents of instructional material in other
Medical interventions used for
children with ASD report more languages as well as be
nonstandard purposes also are
stress544,545 and increased costs546 knowledgeable of other resources in
sometimes prescribed for symptoms
than do parents who do not have their communities that can provide
of ASD. Clinical trials do not support
a child with ASD. More than half of services or support to the culturally
the use of antifungal agents,
families report that a parent needs to diverse groups they serve.
immunotherapy, or hyperbaric
cut back on work or stop working
oxygen treatment, and concern for Comorbid conditions, such as
because of the care needs of the
safety, in addition to lack of intellectual disability and/or
child.547 The largest societal costs
supporting data, cautions against psychiatric disorders, add to the
associated with ASD are special
chelation therapy for children with impact of ASD on family functioning
education, residential care, and lost
ASD.516 and access to care.551 Although
days of caregiver work.4 Peer support
families of older children and youth
As with any intervention, families for families of children with ASD is
typically report fewer interactions
electing a novel therapy should work associated with less parental stress,
with professionals, the stress on the
with their therapeutic team to less negative mood, and more positive
parent related to the ASD diagnosis
identify target symptoms they hope perceptions.548 Parents who
persists.552 Primary care providers
to address and develop a monitoring understand more about their child’s
should speak with families about the
system to track change. Interventions ASD can advocate for more intensive
stresses associated with ASD and the
should be implemented in a stepwise and appropriate services.549 Best
health of other family members and
fashion so that proper attribution of practice includes giving families
make appropriate referrals, either for
effect is possible and confounding contact information for a family
supportive counseling for the
factors can be identified. It is support group at the time of
caregivers or agencies that can
important that the medical home diagnosis. This support may be a local
address behavioral and respite needs
provider and family collaborate to group that provides face-to-face
of the child or to address unmet
select and monitor safe and effective interaction and community activities
health needs in family members.
interventions.542 or an online community.550 Many
families may not have the time or The effect on siblings also needs to be
inclination at the time of diagnosis to considered in the context of both
SECTION 6: WORKING WITH FAMILIES communicate with other families anticipatory guidance and primary
Families play a key role in effective affected by ASD but may find the care. Most siblings of children with
treatment for children with ASD. support useful later when they are ASD do not report having a sibling
Recognition that individuals who are facing the transitions of preschool, with a disability to be a negative
affected and their families are adolescence, or adulthood. National experience; however, they, too, are at
partners with the professionals in all support groups that address a wider risk for increased stress and
aspects of planning a personal, local, community of children and youth subsequent emotional problems.553

Siblings may have precocious time and resources for specialized youth with ASD understand their
involvement in the care of the child care.555,557 Parents of children and diagnosis within the context of their
with ASD, and some resent the youth with ASD would like better developmental level can help them
amount of attention and resources access to specialty care and report understand their symptoms and
the child with ASD requires or the greater unmet medical and behavioral participate in decision-making.562
family’s inability to participate in health care needs558 and a higher
activities in which they see their financial burden for care compared Transition to Adulthood
peers engaging. Proactively teaching with parents of children without
Planning for children with ASD to
siblings about ASD and providing ASD.559
understand and participate in their
them with peer support may be
Increasing family awareness and own health care should begin early in
helpful (Autism Speaks Sibling tool
understanding of the medical home adolescence, with adaptation for
kit: http://www.autismspeaks.org/
can promote partnership of the developmental abilities. The AAP
sites/default/files/a_siblings_guide_
parents and primary care provider in clinical report “Supporting the Health
to_autism.pdf). Many areas have
planning and coordinating the child’s Care Transition From Adolescence to
groups to provide education and
care and advocating for their needs. Adulthood in the Medical Home”
support to siblings. It appears that
National survey data reveal that provides guidance on the steps
positive parental attitudes and
family-centered and coordinated care necessary to address health care
a supportive family setting are
through a medical home results in transitions for all patients with
associated with better sibling
fewer unmet needs,558 including chronic conditions.563 Got Transition
adjustment as well. The pediatrician
dental needs.560 Organizations, such recommends 6 core elements that
should monitor the well-being and
as Family Voices and Family-to- need to be addressed for health care
need for behavioral health supports
Family Health Information Centers, transition without disruption in care,
of siblings as well as parents.
can provide information and support including (1) a transition policy for
Medical Home as well as resources for guiding the practice, (2) tracking and
families in developing care notebooks monitoring transition, (3) assessing
In the AAP’s medical home model,
for their child. Through their ongoing transition readiness for youth and/or
primary care is envisioned as
relationship, providers can help family, (4) actively planning the
accessible, continuous,
children understand their own details of transition, (5) transfer of
comprehensive, family centered,
diagnosis at their developmental care, and (6) transition
coordinated, compassionate, and
level. Clinicians can remind their completion.564 The pediatric health
culturally sensitive for all children
patients with ASD of their strengths, care provider is also in a position to
and youth, including those with
such as focus, memory, visual-spatial advise the family about teaching their
special health care needs. Children
problem-solving, and others, as well adolescent with ASD about
with ASD represent a population that
as their personal accomplishments in sexuality.565 Planning for wellness
has had difficulty accessing
building skills and mastering barriers requires considering young adult
comprehensive coordinated services.
to achieve goals. Recognition of opportunities for exercise and leisure
The chronic care model provides the
achievement of milestones, whether it activities. Planning for medical
structure for clinicians to collaborate
is toilet training or college graduation, transition for all aspects of health
with patients and their families.554
should be acknowledged. care should start around ages 12 to
Parents of children with ASD perceive
14 years. Educational transition starts
care to be less comprehensive, less Shared decision-making promotes
at the school level at age 14 years and
well coordinated, and less family a collaborative process for planning
should involve the student as much as
centered than they desire and report care through dialogue among the
possible.
that they are less satisfied with their individual who is affected, caregivers,
care compared with parents of and clinicians. It can be particularly As a child approaches legal
children with other special health useful when the evidence for an adulthood, the family may need to
care needs.555 Parents also perceive intervention is either controversial or consider guardianship, either full
their providers as less well informed if there is not a uniformly accepted guardianship in cases in which an
regarding treatments for ASD, approach.561 Shared decision-making adult child cannot make health,
especially complementary, requires clarity of the question to be financial, or other decisions because
alternative, and integrative therapies, answered, the options to be of cognitive impairment; limited
than they would like them to be. understood, and the family context guardianship in cases in which an
Pediatricians report that they lack the and beliefs to be respected. It is often individual can participate in decision-
knowledge to provide this support to a process rather than a single making; or conservatorship in cases
patients with ASD556 as well as the conversation. Helping children and in which the oversight extends only to

financial decision-making. Many should initiate discussions with The social services and home- and
young adults with ASD will be parents regarding their plans for community-based waiver services
capable of independent decision- where their child with ASD will available to families whose children
making and should be prepared for progress to postsecondary school have developmental disabilities,
transition to adulthood like other education and/or employment and including ASD, differ from state to
teenagers. The young adult with ASD their plans for where their child will state.568 The clinician should be
may be eligible for Supplemental live in adulthood early in adolescence familiar with the requirements for
Security Income (SSI) benefits. SSI is so the family can plan appropriately programs in their state that might
a federal program that provides funds with community agencies. lead to a Medicaid waiver (medical
for the care of individuals with assistance as a secondary insurance
developmental disabilities who will Families should work with their for children with special health care
not be able to support themselves child’s school throughout adolescence needs), service coordination, respite
independently. Because of the strict to target the skills their child will care, and other financial or behavioral
guidelines regarding cognitive and need to master to be successful in supports afforded a family when
adaptive delays, some adults with young adult programs, the workforce, a child has special health care needs.
ASD may not be eligible for SSI even if or postsecondary education. Goals for The clinician may need to complete
their disability is a barrier to increasing skills may include a form to verify the diagnosis and
employment. Families may wish to academic, social, communication, needs for eligibility. Of note, some
meet with a counselor who can advise leisure, and self-care goals. Families children with ASD who have typical
them on financial planning, with need information to be as proactive cognitive abilities may not qualify for
attention to the needs of an adult as possible in planning for health, many special education and social
child with developmental disability. academic, job, and residential needs service supports. However, later on, at
in young adulthood. Additional the time of transition to adulthood, if
Students with disabilities who plan to
research is needed to develop and they experience difficulty with
continue their education need to be
evaluate evidence-based and effective employment and daily-living skills,
advised of the transitioning process
interventions for this age group.314 they may qualify for support services.
into postsecondary education.
The pediatric health care provider
Students with disabilities are
should provide anticipatory guidance
protected under IDEA (1990; SECTION 7: RESEARCH AND SERVICE
to the family in the context of ongoing
amended 1997 and 2004); Section NEEDS
health supervision and communicate
504 of the Rehabilitation Act of 1973;
with identified adult providers for More than $1.5 billion of private and
the Americans with Disabilities Act
smooth health care transition.567 public research funding was devoted
(1990); and the ADA Amendments
to ASD between 2008 and 2010.569
Act of 2008. Some colleges may
The passage of the Combating Autism
provide accommodations to students State Programs, Supports, and Laws Act of 2006 (Public Law 109–416)
with developmental disabilities with
State laws related to education, social and its reauthorization in 2014 as the
proper documentation of their needs,
service, and insurance for individuals Autism Collaboration, Accountability,
including recent academic testing.
with ASD vary significantly. Although Research, Education and Support Act
College students with ASD may
the federal government mandates (CARES) Act (Public Law 113–157)
benefit from continued supports
early intervention for children at risk continued a trend in funding to
around social skills development,
for developmental delay and a free address the intervention needs of
medication monitoring, and
and appropriate education for individuals diagnosed with ASD.
mentoring on living independently.566
students aged 3 to 21 years who have Before this time, research funding
Although resources are still specific educationally handicapping was largely focused on the genetics
insufficient, attention is growing for conditions, the implementation of and neurobiology of the disorder.
the need to provide social skills educational services varies by state However, this changed with the
training for youth with ASD with and and locality. The law states that convening of the National Institutes
without intellectual disabilities to services need to be appropriate, not of Health Interagency Autism
enter the workforce in competitive necessarily optimal. No legal mandate Coordinating Committee in 2006. The
employment as well as job skill for adult services exists, although the committee was assembled to provide
development. There are insufficient agencies that provide residential guidance to the agencies funding
group-home and supported services, service coordination, job autism services, and the research
community–living arrangements for training, and adult day services agenda was expanded on the basis of
adults with ASD to meet the demands typically are funded through the the contributions of stakeholders,
in most communities. The clinician states. including families, individuals

affected, and federal agencies. The Research in all of these areas is postsecondary work or schooling,
committee’s 2009 strategic plan, critical to move forward with early residential supports, and activities
updated in 2017,570 identified 7 areas diagnosis, effective treatment, and to maintain a healthy lifestyle.
for research funding: (1) early evidence-based interventions at • Informed individuals and families:
detection, (2) underlying biology, (3) each age. The pediatrician can educate youth
genetic and environmental risk with ASD and their families about
factors, (4) treatments and the evidence for interventions,
interventions, (5) services and PEDIATRIC RECOMMENDATIONS
refer families for possible
implementation science, (6) lifespan To provide appropriate care to all participation in clinical research
services and supports, and (7) children and families affected by ASD, when appropriate, refer families to
epidemiological surveillance and health, education, and public health support organizations, and
infrastructure.571 The committee systems need to collaborate and build prepare families to navigate
recommended that multiple levels of integrated and adequately funded and transitions.
inquiry be pursued simultaneously to staffed systems. • Informed pediatric providers: To
inform evidence-based clinical care. • Early identification and best serve patients and families
These levels include the following: treatment: Pediatric providers affected by ASD, the clinician caring
• basic and translational science in should use screening and for children and youth with ASD
the areas of genetics and surveillance to provide accurate should be familiar with issues
epigenetics, neurobiology, and and early identification, cost- related to diagnosis, coexisting
psychopharmacology to effective and timely diagnosis, medical and behavioral conditions,
understand typical and atypical prompt implementation of and the impact of ASD on the family
brain development and function to evidence-based interventions, and to provide a medical home for these
develop ASD-specific behavioral elimination of disparities to patients. Actively addressing
and pharmacologic therapies; access to care for children with capacity building to care for
ASD. Clinicians should respond children and youth with ASD
additional research is needed to
appropriately to family or clinical requires initiatives directed at
identify and understand ASD risk
concerns and results of screening provider education and practice
factors that might be mitigated to
to avoid delays in diagnosis and quality improvement and public
reduce ASD-related disability;
treatment. health, educational, and social
• research into the underlying programs to support families in
• Collaboration of systems of care:
neurobiology of sensory symptoms their journey from diagnosis to
Children with ASD should be
and restricted interests and service provision to transition to
provided evidence-based services
repetitive behaviors to inform adult care.
to address social, academic, and
development of targeted
behavioral needs at home and
interventions;
school; access to appropriate LEAD AUTHORS
• clinical trials to test focused pediatric and mental health care;
interventions based on the Susan L. Hyman, MD, FAAP
respite services; and leisure Susan E. Levy, MD, MPH, FAAP
underlying biological processes activities. Scott M. Myers, MD, FAAP
involved with ASD to determine if
• Planning for adolescence and
they are appropriate for
transition to adult systems of care: CONTRIBUTORS
community application;
Communities should build services
• epidemiological surveillance to to promote social skills appropriate
Paul H. Lipkin, MD, FAAP
Michelle M. Macias, MD, FAAP
gather data important for planning for work and postsecondary
for current and future needs, education, access to appropriate
including screening, diagnosis, and medical and behavioral health EDITOR
lifespan health and mental health services, job skills development, Anne B. Rodgers
services; and and community leisure
• health services research to provide opportunities. Pediatricians need to
COUNCIL ON CHILDREN WITH DISABILITIES
guidance for comprehensive, engage with families and youth to
EXECUTIVE COMMITTEE, 2019–2020
accessible, and culturally plan a transition to adult medical
Dennis Z. Kuo, MD, MHS, FAAP, Chairperson
appropriate medical, educational, and behavioral health care. The
Susan Apkon, MD, FAAP
and behavioral care for children, medical home provider should Lynn F. Davidson, MD, FAAP
youth, adults, and families affected support the family and youth in Kathryn A. Ellerbeck, MD, FAAP
by ASD. advocating for appropriate Jessica E.A. Foster, MD, MPH, FAAP

Susan L. Hyman, MD, FAAP Marshalyn Yeargin-Allsopp, MD, FAAP – PAST SECTION ON DEVELOPMENTAL AND
Garey H. Noritz, MD, FAAP Centers for Disease Control and Prevention BEHAVIORAL PEDIATRICS EXECUTIVE
Mary O’Connor Leppert, MD, FAAP COMMITTEE MEMBERS
Barbara S. Saunders, DO, FAAP
Christopher Stille, MD, MPH, FAAP STAFF Nerissa S. Bauer, MD, MPH, FAAP
Larry Yin, MD, MSPH, FAAP Edward Goldson, MD, FAAP
Alexandra Kuznetsov, RD akuznetsov@
Michelle M. Macias, MD, FAAP
aap.org
Laura Joan McGuinn, MD, FAAP
PAST COUNCIL ON CHILDREN WITH
DISABILITIES EXECUTIVE COMMITTEE SECTION ON DEVELOPMENTAL AND
MEMBERS BEHAVIORAL PEDIATRICS EXECUTIVE
LIAISONS
Timothy Brei, MD, FAAP COMMITTEE, 2018–2019
Beth Ellen Davis, MD, MPH, FAAP Marilyn Augustyn, MD, FAAP – Society for
Carol C. Weitzman, MD, FAAP, Chairperson
Susan E. Levy, MD, MPH, FAAP Developmental and Behavioral Pediatrics
David Omer Childers Jr, MD, FAAP
Paul H. Lipkin, MD, FAAP Beth Ellen Davis, MD, MPH, FAAP – Council
Jack M. Levine, MD, FAAP
Scott M. Myers, MD, FAAP on Children With Disabilities
Myriam Peralta-Carcelen, MD, MPH, FAAP
Kenneth Norwood Jr, MD, FAAP, Immediate Alice Meng, MD – Section on Pediatric
Jennifer K. Poon, MD, FAAP
Past Chairperson Trainees
Peter J. Smith, MD, MA, FAAP
Pamela C. High, MD, MS, FAAP – Former
Nathan Jon Blum, MD, FAAP, Immediate Past
liaison, Society for Developmental and
Chairperson
LIAISONS Behavioral Pediatrics
John Ichiro Takayama, MD, MPH, FAAP,
Cara Coleman, MPH, JD – Family Voices Website Editor
Marie Mann, MD, MPH, FAAP – Maternal and Rebecca Baum, MD, FAAP, Section Member,
Child Health Bureau Committee on Psychosocial Aspects of Child
STAFF
Edwin Simpser, MD, FAAP – Section on and Family Health
Home Care Robert G. Voigt, MD, FAAP, Newsletter Editor Carolyn McCarty, PhD
Peter J. Smith, MD, MA, FAAP – Section on Carolyn Bridgemohan, MD, FAAP, Program [email protected]
Developmental and Behavioral Pediatrics Chairperson Linda Paul, MPH [email protected]
ABBREVIATIONS DSM-5: Diagnostic and Statistical NDBI: naturalistic developmental

AAC: augmentative and alternative Manual of Mental Disorders, behavioral intervention
communication Fifth Edition OCD: obsessive-compulsive
AAP: American Academy of DSM-IV: Diagnostic and Statistical disorder
Pediatrics Manual of Mental Disorders, PDD: pervasive developmental
ABA: applied behavior analysis Fourth Edition disorder
ADDM: Autism and Developmental DSM-IV-TR: Diagnostic and Statistical PDD-NOS: pervasive developmental
Disabilities Monitoring Manual of Mental disorder not otherwise
ADHD: attention-deficit/ Disorders, Fourth Edition, specified
hyperactivity disorder Text Revision RCT: randomized controlled trial
ADI-R: Autism Diagnostic ESDM: Early Start Denver Model SCQ: Social Communication
Inventory-Revised GI: gastrointestinal Questionnaire
ADOS-2: Autism Diagnostic IDEA: Individuals with Disabilities SRS: Social Responsiveness Scale
Observation Schedule, Education Improvement Act SSI: Supplemental Security Income
Second Edition of 2004 SSRI: selective serotonin reuptake
ASD: autism spectrum disorder IEP: Individualized Education inhibitor
CARS-2: Childhood Autism Rating Program STAT: Screening Tool for Autism in
Scale, Second Edition LEAP: Learning Experiences and Toddlers and Young Children
CDC: Centers for Disease Control Alternative Programs for TEACCH: Treatment and Education
and Prevention Preschoolers and their Parents of Autistic and Related
CMA: chromosomal microarray M-CHAT: Modified Checklist for Communication-
CNV: copy number variant Autism in Toddlers Handicapped Children
CTM: comprehensive treatment model M-CHAT-R/F: Modified Checklist for USPSTF: US Preventive Services
DSM: Diagnostic and Statistical Autism in Toddlers, Task Force
Manual of Mental Disorders Revised with WES: whole-exome sequencing
Follow-Up (Questions)

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2020 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: MeMix LLC is a company that makes an application (for phones). Dr Levy is on the advisory board for the application’s
development. This application is being developed to assist in nutritional and dietary management of children with autism. Dr Levy has not received any money yet
from this company. This application is the focus of a National Institutes of Health R21 grant, for which Dr Levy is funded for ∼2% of her salary. Once it is studied and
marketed (if appropriate), Dr Levy will (possibly in the future) earn some money. Her years of relationship with the company are 2015 to the present. Dr Hyman has
a relationship with Roche. Dr Hyman is the site principal investigator of a clinical trial of a novel agent being tested to promote social function in patients with
autism. The University of Rochester (Dr Hyman’s institution) was 1 of .40 sites and had 2 study participants in 2018. University of Rochester will be leaving the trial
in 2019 (withdrawal submitted) because of staffing, and that reimbursement for staff time does not cover the cost of participation. Funding was for the staff to
complete the assessments required for the clinical trial. Dr Hyman got no personal reimbursement from the company; the funding was for staff time for
recruitment and assessment and clinical research center support for the trial.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-3448.
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Supplemental Information
SUPPLEMENTAL TABLE 14 Recurrent CNVs Most Commonly Identified in Cohorts With ASD by Using CMA Analysis
CNV Region Frequencya Common Clinical Features
16p11.2 deletion 1 in 304 ASD, DD or ID, expressive language impairment, relative or absolute
macrocephaly, overweight
16p11.2 duplication 1 in 396 ASD, schizophrenia, bipolar disorder, ADHD, relative or absolute microcephaly,
underweight
15q11.2-q13 (BP2–BP3) duplication 1 in 494 ASD, DD or ID, epilepsy, hypotonia, ataxia, behavior problems
15q13.2-q13.3 (BP4–BP5) deletion 1 in 659 ASD, DD or ID, epilepsy, schizophrenia, cardiac defects
1q21.1 duplication 1 in 659 ASD, DD or ID, schizophrenia, ADHD, relative macrocephaly, hypertelorism
22q11.2 duplication 1 in 659 ASD, DD or ID, hypotonia, motor delay
16p13.11 deletion 1 in 791 ASD, DD or ID, epilepsy, schizophrenia, congenital anomalies
7q11.23 duplication 1 in 989 ASD, DD or ID, growth retardation, hypotonia
16p12.2 deletion 1 in 989 ASD, DD or ID, schizophrenia, epilepsy, growth retardation, cardiac defects,
microcephaly, hypotonia
17q12 deletion 1 in 1978 ASD, DD or ID, schizophrenia, renal cysts, mature-onset diabetes of the young
type 5
15q13.2–13.3 (BP4–BP5) duplication 1 in 1978 ASD, DD or ID, obesity
BP2 breakpoint 2; BP3 breakpoint 3; BP4 breakpoint 4; BP5 breakpoint 5; DD developmental delay; ID intellectual disability.
a Moreno-De-Luca D et al631; the frequency of each CNV among 3955 probands with ASD from the Autism Genetic Resource Exchange, Autism Genome Project, and Simons Foundation
Autism Research Initiative Simplex Collection cohorts.
PEDIATRICS Volume 145, Number 1, January 2020 1

2
SUPPLEMENTAL TABLE 13 Selected Genetic Syndromes Associated With ASD
Condition Physical Findings Gene Confirmatory Testing Importance
Fragile X syndrome Long face, prominent forehead and jaw, FMR1 (CGG repeat Targeted mutation analysis (PCR and Genetic counseling (X-linked dominant
large ears, joint laxity, macroorchidism expansion, abnormal Southern blot) inheritance); all mothers of individuals
after puberty in boys methylation) with an FMR1 full mutation are carriers
of an FMR1 premutation or full
mutation; extended family counseling is
necessary; premutation carriers are at
risk for fragile X–associated tremor/
ataxia syndrome and FMR1-related
primary ovarian insufficiency in female
patients; several targeted
pharmacologic therapies are under
investigation
Neurofibromatosis 1 Multiple café-au-lait macules, axillary and NF1 Clinical criteria; optimized protein Genetic counseling (autosomal dominant
inguinal freckling, iris Lisch nodules, truncation testing, sequence analysis, inheritance); 50% de novo, 50%
cutaneous neurofibromas and deletion or duplication analysis are inherited; associated problems
available but infrequently required requiring investigation or monitoring
(optic gliomas, other CNS tumors,
peripheral nerve sheath tumors,
vasculopathy, hypertension, orthopedic
issues, osteopenia)
PTEN hamartoma tumor syndrome (includes Marked macrocephaly, skin hamartomas, PTEN PTEN sequence analysis, deletion or Genetic counseling (autosomal dominant
Cowden syndrome and pigmented macules of the glans penis duplication analysis inheritance with highly variable
Bannayan-Riley-Ruvalcaba syndrome) expression); associated problems
requiring investigation or monitoring
(significant risk of benign and
malignant tumors of the thyroid,
breast, and endometrium as well as
intestinal polyps, colorectal cancer,
renal cell carcinoma, cutaneous
melanoma, and cerebellar dysplastic
gangliocytoma)
Rett syndrome Deceleration of head growth velocity, MECP2 MECP2 sequence analysis, deletion or Genetic counseling (.99% de novo, ,1%
acquired microcephaly, loss of duplication analysis germline mosaicism); associated
purposeful hand use, prominent hand problems requiring investigation or
stereotypies (especially hand wringing monitoring and anticipatory guidance

or clasping), apraxia, hyperventilation (failure to thrive, gastroesophageal
or breath-holding, seizures reflux, respiratory problems,
osteopenia, sudden death); targeted
pharmacologic therapy under
investigation
Smith-Lemli-Opitz syndrome Characteristic facial features (narrow DHCR7 7-dehydrocholesterol level (elevated); DHCR7 Genetic counseling (autosomal recessive
forehead, low-set ears, ptosis, sequence analysis available inheritance); potential role for
epicanthal folds, short nose, treatment with cholesterol
anteverted nares), microcephaly, cleft
palate, 2- to 3-toe syndactyly, postaxial
polydactyly, hypospadias in male
SUPPLEMENTAL TABLE 13 Continued
Condition Physical Findings Gene Confirmatory Testing Importance
patients, prenatal and postnatal
growth retardation
Timothy syndrome Long QT interval, other ECG abnormalities CACNA1C Targeted mutation analysis, sequence Genetic counseling, autosomal dominant,
(atrioventricular block, macroscopic analysis, deletion or duplication analysis usually de novo, but parental germline
T-wave alternans), congenital heart mosaicism has been observed;
defects, cutaneous syndactyly, low-set treatment related to long QTc
ears, flat nasal bridge, thin upper lip, (b-blocker, pacemaker, implantable
round facies, baldness for the first 2 y defibrillator) and avoidance of
of life followed by thin scalp hair, hypoglycemia
dental abnormalities, frequent
infections because of altered immune
response, intermittent hypoglycemia
PEDIATRICS Volume 145, Number 1, January 2020

Tuberous sclerosis Hypopigmented macules, angiofibromas, TSC1, TSC2 Clinical criteria; TSC1 and TSC2 sequencing Genetic counseling (autosomal dominant
shagreen patches (connective tissue available inheritance); associated problems
nevi), ungual fibromas, retinal requiring investigation or monitoring
hamartomas (CNS tumors, seizures, renal
angiomyolipomas or cysts, cardiac
rhabdomyomas and arrhythmias);
potential role for targeted
pharmacologic therapy (mTOR
inhibitors)
CACNA1C, calcium channel, voltage-dependent, L-type, a-1c subunit; CGG, cytosine-guanine-guanine; CNS, central nervous system; DHCR7, 7-dehydrocholesterol reductase; ECG, electrocardiogram; FMR1, fragile X mental retardation 1; MECP2, methyl
CpG binding protein 2; mTOR, mammalian target of rapamycin; PCR, polymerase chain reaction; PTEN, phosphatase and tensin homolog; QTc, corrected QT interval; TSC1, tuberous sclerosis 1; TSC2, tuberous sclerosis 2. Adapted with permission
from Myers SM, Challman TD. Autism Spectrum Disorders. In: Voigt RG, Macias MM, Myers SM, eds. Developmental and Behavioral Pediatrics. Elk Grove Village, IL: American Academy of Pediatrics; 2011:249–291.

3
SUPPLEMENTAL TABLE 15 Selected ASD Risk Genes Identified or Confirmed in Whole-Exome Studies
Gene Gene Name Broad Functional Categorization
SCN2A sodium channel, voltage-gated, type II, a subunit Synaptic functions (eg, ion channels, neurotransmitter receptors, cell adhesion
GRIN2B glutamate receptor, ionotropic, N-methyl-D-aspartate 2B molecules, microtubule assembly, scaffolding proteins, actin cytoskeleton)
KATNAL2 katanin p60 subunit A-like 2
ANK2 ankyrin 2, neuronal
DSCAM Down syndrome cell adhesion molecule
NRXN1 neurexin 1
SHANK2 SH3 and multiple ankyrin repeat domains 2
SHANK3 SH3 and multiple ankyrin repeat domains 3
PTEN phosphatase and tensin homolog Intracellular signaling, activity-dependent synaptic protein synthesis and
SYNGAP1 synaptic Ras GTPase activating protein 1 degradation
DYRK1A dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A
POGZ pogo transposable element with ZNF domain
CUL3 cullin 3
CHD2 chromodomain helicase DNA binding protein 2 Transcription regulation, chromatin remodeling
CHD8 chromodomain helicase DNA binding protein 8
ADNPa activity-dependent neuroprotector homeobox
ARID1B AT rich interactive domain 1B (SWI1-like)
ASH1L ASH1 (absent, small, or homeotic)-like
KDM5B lysine-specific demethylase 5B
KMT2C lysine-specific methyltransferase 2C
SETD5 SET domain containing 5
TBR1 T-box, brain, 1
Based on de novo loss of function variants and small de novo deletions (false discovery rate , 0.01). Adapted from Sanders SJ, He X, Willsey AJ, et al; Autism Sequencing Consortium.
Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci. Neuron. 2015;87(6):1215–1233; Krumm N, O’Roak BJ, Shendure J, Eichler EE. A de novo
convergence of autism genetics and molecular neuroscience. Trends Neurosci. 2014;37(2):95–105; Brandler WM, Sebat J. From de novo mutations to personalized therapeutic interventions
in autism. Annu Rev Med. 2015;66:487–507; De Rubeis S, He X, Goldberg AP, et al; DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium. Synaptic, transcriptional
and chromatin genes disrupted in autism. Nature. 2014;515(7526):209–215; Bourgeron T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev
Neurosci. 2015;16(9):551–563; and Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;
485(7397):237–241.
a Also involved in microtubule dynamics at the synapse.
4
SUPPLEMENTAL TABLE 16 Selected Metabolic Conditions That May (Rarely) Be Associated With an ASD Phenotype
Disorders of amino acid metabolism
Phenylketonuria (untreated)
Homocystinuria
Branched-chain ketoacid dehydrogenase kinase deficiency
Disorders of g-aminobutyric acid metabolism
Succinic semialdehyde dehydrogenase deficiency
Disorders of cholesterol metabolism
Smith-Lemli-Opitz syndrome (7-dehydrocholesterol reductase deficiency)
Disorders associated with cerebral folate deficiency
Folate receptor 1 gene mutations
Dihydrofolate reductase deficiency
Disorders of creatine transport or metabolism
Arginine-glycine amidinotransferase deficiency
Guanidinoacetate methyltransferase deficiency
X-linked creatine transporter deficits
Disorders of carnitine biosynthesis
6-N-trimethyllysine dioxygenase deficiency
Disorders of purine and pyrimidine metabolism
Adenylosuccinate lyase deficiency
Adenosine deaminase deficiency
Cytosolic 59-nucleotidase superactivity
Dihydropyrimidine dehydrogenase deficiency
Phosphoribosyl pyrophosphate synthetase superactivity
Lysosomal storage disorders
Sanfilippo syndrome (mucopolysaccharidosis type III)
Mitochondrial disorders
Mitochondrial DNA mutations
Nuclear DNA mutations
Others
Biotinidase deficiency
Urea cycle defects
Adapted from Schaefer GB, Mendelsohn NJ; Professional Practice and Guidelines Com-
mittee. Clinical genetics evaluation in identifying the etiology of autism spectrum dis-
orders: 2013 guideline revisions. Genet Med. 2013;15(5):399–407; Legido A, Jethva R,
Goldenthal MJ. Mitochondrial dysfunction in autism. Semin Pediatr Neurol. 2013;20(3):
163–175; Jiang YH, Wang Y, Xiu X, Choy KW, Pursley AN, Cheung SW. Genetic diagnosis of
autism spectrum disorders: the opportunity and challenge in the genomics era. Crit Rev
Clin Lab Sci. 2014;51(5):249–262; and Frye RE. Metabolic and mitochondrial disorders
associated with epilepsy in children with autism spectrum disorder. Epilepsy Behav. 2015;
47:147–157.
SUPPLEMENTAL REFERENCES data sets to infer pathogenicity for cohorts. Mol Psychiatry. 2013;18(10):
rare copy number variants in autism 1090–1095
631. Moreno-De-Luca D, Sanders SJ,
Willsey AJ, et al. Using large clinical
PEDIATRICS Volume 145, Number 1, January 2020 5

Identification, Evaluation, and Management of Children With Autism Spectrum
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Identification, Evaluation, and Management of Children With Autism Spectrum
Disorder
Susan L. Hyman, Susan E. Levy, Scott M. Myers and COUNCIL ON CHILDREN
WITH DISABILITIES, SECTION ON DEVELOPMENTAL AND BEHAVIORAL
PEDIATRICS
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CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care

Identiﬁcation, Evaluation, and

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder abstract

To cite: Hyman SL, Levy SE, Myers SM, AAP COUNCIL ON

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TABLE 3 DSM-5 Social (Pragmatic) Communication Disorder (DSM-5 315.39)

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PEDIATRICS Volume 145, number 1, January 2020

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FROM THE AMERICAN ACADEMY OF PEDIATRICS

PEDIATRICS Volume 145, number 1, January 2020

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TABLE 10 Considerations Surrounding Medication Use

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ABBREVIATIONS DSM-5: Diagnostic and Statistical NDBI: naturalistic developmental

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