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176 Part III Behavioral and Psychiatric Disorders

Chapter

30

Autism Spectrum
Disorder
Giuseppe J. Raviola, Michael L. Trieu,
David R. DeMaso, and Heather J. Walter
The essential features of autism spectrum disorder (ASD) are persistent impairment in reciprocal social communication and interaction,
and restricted, repetitive patterns of behavior or interests (Table 30-1).
ASD encompasses disorders previously referred to as early infantile
autism, childhood autism, Kanner autism, high functioning autism,
atypical autism, Asperger disorder, childhood disintegrative disorder,
and pervasive developmental disorder not otherwise specified. These
specific diagnoses are not reliably distinguishable or consistently
applied across different treatment centers. Individuals diagnosed with
one of these previous diagnoses should be given the diagnosis of ASD.

DESCRIPTION
Social Communication and Interaction Deficits

Aberrant development of social communication and impaired ability


to engage in reciprocal social interactions are hallmark symptoms of
ASD. Deficits in socialemotional reciprocity (the ability to engage
with others and share thoughts and feelings) are evident early in children with ASD who show little or no initiation of social interaction
and little or no sharing of emotions or imitative behaviors. Children
may present with abnormal social approach, failure of back-and-forth
conversation, and difficulties processing and responding to complex
social cues. Infants <6mo of age may or may not demonstrate features
typical of ASD.
Impairments in nonverbal social communication are manifested by
absent, reduced, or atypical use of eye contact, gestures, facial expressions, body orientation, or speech intonation. Youth may fail to smile,
orient to name, or use gestures to point or show. Abnormal eye contact
with failure to follow someones pointing or eye gaze is characteristic.
In patients with fluent language, poorly integrated verbal and nonverbal communication may result in odd, wooden, or exaggerated body
language during social interactions (Table 30-2).
Children with ASD may demonstrate absent, reduced, or atypical
social interest, manifested by rejection of others, passivity, or inappropriate approaches that seem aggressive and disruptive. In young
children, lack of shared, age-appropriate flexible pretend and symbolic
play is seen, with children often insistent on playing by very fixed rules.

Chapter 30 Autism Spectrum Disorder 177


Table 30-1 DSM-5 Diagnostic Criteria for Autism
Spectrum Disorder
A. Persistent deficits in social communication and social interaction
across multiple contexts, as manifested by the following,
currently or by history:
1. Deficits in social-emotional reciprocity.
2. Deficits in nonverbal communicative behaviors used for social
interaction.
3. Deficits in developing, maintaining, and understanding
relationships.
B. Restricted, repetitive patterns of behavior, interests, or activities,
as manifested by at least two of the following, currently or by
history:
1. Stereotyped or repetitive motor movements, use of objects,
or speech.
2. Insistence on sameness, inflexible adherence to routines, or
ritualized patterns of verbal or nonverbal behavior.
3. Highly restricted, fixated interests that are abnormal in
intensity or focus.
4. Hyper- or hyporeactivity to sensory input or unusual interest
in sensory aspects of the environment.
C. Symptoms must be present in the early developmental period
(may not become fully manifest until social demands exceed
limited capacities, or may be masked by learned strategies in
later life).
D. Symptoms cause clinically significant impairment in social,
occupational, or other important areas of current functioning.
E. These disturbances are not better explained by intellectual
disability (intellectual developmental disorder) or global
developmental delay.
Adapted from the Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition, (Copyright 2013). American Psychiatric Association, pp. 5051.

Children with ASD may prefer solitary activities and interactions with
much younger or older people. A desire to establish friendships without
complete understanding of the components of friendship (one-sided
friendships based solely on shared special interests) can be seen in
some children, while an absence of interest in peers may be seen in
others. Some youth show deficits in empathy and understanding what
another person might be thinking.

Restricted and Repetitive Patterns

The second core characteristic of ASD is restricted, repetitive patterns


of behavior, interests, or activities. These include stereotyped movements (hand flapping, finger flicking), repetitive use of objects (spinning coins, lining up toys), repetitive and abnormal speech (echolalia
[delayed or immediate parroting of heard words], pronoun reversal,
nonsense rhyming, idiosyncratic phrases); insistence on sameness and
inflexible adherence to routines or ritualized patterns of behavior (distress at small changes, insistence on adherence to rules, rituals and
routines, rigid thinking, repetitive questioning); highly restricted and
fixed interests of abnormal intensity or focus (e.g., strong attachment
to or preoccupation with unusual objects, excessively circumscribed or
perseverative interests); and hyper- or hyporeactivity to sensory input
or unusual interest in sensory aspects of the environment (e.g., extreme
responses to specific sounds or textures, excessive smelling or touching
of objects, fascination with lights or spinning objects, apparent indifference to pain, heat, or cold) (see Table 30-2).
The symptoms of ASD must be present in the early developmental
period, must cause clinically significant functional impairment, and
must not be better explained by intellectual disability or global developmental delay.

Severity

The severity of ASD is based on evaluations of impairment caused by


both deficits in social communication and in restricted, repetitive
behaviors. Within these 2 categories, severity is rated levels 1-3, with

level 3 implying most severe deficit with a need for the most substantial
support (Table 30-3).

Specifiers/Associated Features

ASD is specified as occurring with or without accompanying intellectual and language impairment, and associated with a known medical
or genetic condition, environmental factor, or other neurodevelopmental, mental, or behavioral disorder. Children with ASD vary in
their verbal abilities. Language level in individuals with ASD without
accompanying language impairment may speak in full sentences or
have fluent speech. ASD specified with accompanying language
impairment can range from nonverbal speech to single word or phrase
speech (capable of imitating songs, rhymes, or television commercials).
Receptive language may lag behind expressive language development
in ASD. Early abnormal language concerns include absent babbling or
gestures by 12mo, absent single words by 16mo, and absent 2-word
purposeful phrases by 24mo, as well as any loss of language or social
skills at any time. Language, if present, is often one-sided, lacking social
reciprocity, idiosyncratic, repetitive, and used to request or label rather
than comment, share feelings, or converse.
Intellectual functioning can vary from intellectual impairment
(intellectual developmental disorder) to superior intellectual functioning in select areas (splinter skills, savant behavior) (with or without
accompanying intellectual impairment). Some children show typical
development in certain skills and can even show areas of strength in
specific areas (puzzles, art, or music). The intellectual profile of an
individual may be uneven, with gaps in verbal and nonverbal learning
ability and intellectual and adaptive functional skills.
Motor deficits, including odd gait, clumsiness, dyspraxia, and other
abnormal motor signs (e.g., walking on tiptoes) are often present.
Stereotypic movement or tic disorders may go unnoticed given aforementioned restricted behavioral patterns. Self-injury (head banging,
biting the wrist) may occur. Some youth develop catatonic-like motor
behavior (slowing and freezing mid-action) though most do not go
onto develop a full episode with mutism, posturing, grimacing, and
waxy flexibility.
Epilepsy is a common comorbidity, and any type of seizure may be
observed in ASD. Epilepsy is associated with greater intellectual disability and lower verbal ability. Mutations in the BCKD-kinase gene is
a syndrome associated with autism, epilepsy and intellectual disability.
Youth with ASD are also prone to anxiety and depression as well as
abnormalities in attention and hyperactivity.
Language, social, or a mixed pattern of regression may occur in the
first 1-2 years. In some, a diagnosis of Landau Kleffner syndrome is
identified; in others regression may be due to the onset of epilepsy or
abnormal EEG findings in the absence of clinical seizures. Levetiracetam also causes a reversible autistic regression syndrome.

EPIDEMIOLOGY

The Centers for Disease Control and Prevention estimates the prevalence of ASD in the United States as 11.3/1,000 (prior estimated prevalence range: 0.7/10,000 to 72.6/10,000 across 36 earlier surveys). Recent
higher reported rates of the disorder appear to be related to differences
in diagnostic criteria and practices, inclusion of subthreshold cases, age
of children screened, and location of the study. The male:female ratio
is estimated to be 4:1. The incidence of ASD may be higher in immigrant populations.

ETIOLOGY/RISK FACTORS
Genetic and Familial Factors

There is a high recurrence risk (2-19%) for ASD among siblings, as well
as a higher concordance rate (37-90%) in twin studies. Closer spacing
of pregnancies, advanced maternal or paternal age, and extremely
premature birth (<26wk gestational age) as well as family members
with learning problems, psychiatric disorders, and social disability,
have been identified as risk factors. Multiple genes are viewed as
involved in autism with studies supporting a role for both common
(>5% of general population) and rare genetic variations contributing
to the disorder. For example, Timothy syndrome, characterized by

178 Part III Behavioral and Psychiatric Disorders


Table 30-2 Signs and Symptoms of Possible Autism in Preschool Children (or Equivalent Mental Age)
Social interaction and reciprocal communication behaviors
Spoken language
Language delay (in babble or wordsfor example, using fewer than
10 words by the age of 2yr)
Regression in or loss of use of speech
Spoken language (if present) may include unusual features, such as:
vocalizations that are not speech-like; odd or flat intonation;
frequent repetition of set words and phrases (echolalia); reference
to self by name or you or she or he beyond age 3yr
Reduced and/or infrequent use of language for communicationfor
example, use of single words, although able to speak in sentences
Responding to others
Absent or delayed response to name being called, despite normal
hearing
Reduced or absent responsive social smiling
Reduced or absent responsiveness to other peoples facial
expressions or feelings
Unusually negative response to the requests of others (demand
avoidance behavior)
Rejection of cuddles initiated by parent or carer, although the child
himself or herself may initiate cuddles
Interacting with others
Reduced or absent awareness of personal space, or unusually
intolerant of people entering their personal space
Reduced or absent social interest in others, including children of his
or her own agemay reject others; if interested in others, he or she
may approach others inappropriately, seeming to be aggressive or
disruptive
Reduced or absent imitation of others actions
Reduced or absent initiation of social play with others, plays alone
Reduced or absent enjoyment of situations that most children
likefor example, birthday parties
Reduced or absent sharing of enjoyment

Eye contact, pointing, and other gestures


Reduced or absent use of gestures and facial expressions to
communicate (although may place an adults hand on objects)
Reduced and poorly integrated gestures, facial expressions, body
orientation, eye contact (looking at peoples eyes when speaking),
and speech used in social communication
Reduced or absent social use of eye contact (assuming adequate
vision)
Reduced or absent joint attention (when 1 person alerts another
to something by means of gazing, finger pointing, or other verbal
or nonverbal indication for the purpose of sharing interest). This
would be evident in the child from lack of:
Gaze switching
Following a point (looking where the other person points
tomay look at hand)
Using pointing at or showing objects to share interest
Ideas and imagination
Reduced or absent imagination and variety of pretend play
Unusual or restricted interests and/or rigid and repetitive behaviors
Repetitive stereotypical movements such as hand flapping; body
rocking while standing; spinning; finger flicking
Repetitive or stereotyped playfor example, opening and closing
doors
Over focused or unusual interests
Excessive insistence on following own agenda
Extremes of emotional reactivity to change or new situations;
insistence on things being the same
Over-reaction or under-reaction to sensory stimuli, such as textures,
sounds, smells
Excessive reaction to the taste, smell, texture, or appearance of
food, or having extreme food fads

From Baird G, Douglas HR, Murphy MS: Recognizing and diagnosing autism in children and young people: summary of NICE guidance. BMJ 343:d6360, 2011, Box 1,
p. 901.

Table 30-3 DSM-5 Severity Levels for Autism Spectrum Disorder


SEVERITY LEVEL

SOCIAL COMMUNICATION

RESTRICTED, REPETITIVE BEHAVIORS

Level 3
Requiring very
substantial support

Severe deficits in verbal and nonverbal social communication


skills cause severe impairments in functioning, very limited
initiation of social interactions, and minimal response to social
overtures from others. For example, a person with few words
of intelligible speech who rarely initiates interaction and, when
he or she does, makes unusual approaches to meet needs
only and responds to only very direct social approaches

Inflexibility of behavior, extreme difficulty


coping with change, or other restricted/
repetitive behaviors markedly interfere with
functioning in all spheres. Great distress/
difficulty changing focus or action.

Level 2
Requiring substantial
support

Marked deficits in verbal and nonverbal social communication


skills; social impairments apparent even with supports in place;
limited initiation of social interactions; and reduced or
abnormal responses to social overtures from others. For
example, a person who speaks simple sentences, whose
interaction is limited to narrow special interests, and who has
markedly odd nonverbal communication

Inflexibility of behavior, difficulty coping with


change, or other restricted/repetitive
behaviors appear frequently enough to be
obvious to the casual observer and
interfere with functioning in a variety of
contexts. Distress and/or difficulty
changing focus or action.

Level 1
Requiring support

Without supports in place, deficits in social communication


cause noticeable impairments. Difficulty initiating social
interactions, and clear examples of atypical or unsuccessful
responses to social overtures of others. May appear to have
decreased interest in social interactions. For example, a person
who is able to speak in full sentences and engages in
communication but whose to-and-fro conversation with others
fails, and whose attempts to make friends are odd and
typically unsuccessful

Inflexibility of behavior causes significant


interference with functioning in one or
more contexts. Difficulty switching
between activities. Problems of
organization and planning hamper
independence.

From the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association, p. 52.

Chapter 30 Autism Spectrum Disorder 179


dysmorphic facies, congenital heart disease, prolonged QT interval,
and developmental delay, is caused by a mutation in the L-type calcium
channel Cav1.2 and also has ASD features. In addition, ASD is associated with multiple abnormalities of mitochondrial DNA.

Neurobiologic Factors

The high rates of seizure disorder suggest a role for neurobiologic


factors in ASD. The number of different areas of the brain affected by
autism suggests a diverse and widely distributed set of affected neural
systems. Postmortem studies reveal various abnormalities, particularly
within the limbic system. Structural MRI reveals an overall increase of
brain size, and diffusion tensor imaging studies suggest aberrations in
white matter tract development. Functional MRI identifies difficulties
in tasks involving social and affective judgments and differences in the
processing of face and nonface stimuli. Poor neuronal connectivity in
various brain regions also is reported. Elevated peripheral levels of
serotonin are a replicated neurochemical finding of unclear significance. A role for dopamine is suggested given the problems with overactivity and stereotyped mannerisms and the positive response of such
behaviors to antipsychotic medications.
Neuropsychological correlates of ASD include impairments in executive functioning (e.g., simultaneously engaging in multiple tasks),
weak central coherence (integrating information into meaningful
wholes), and deficits in theory of mind tasks (taking the perspective of
another person). The empathizing-systemizing personality theory
describes the autistic mind in terms of impaired empathy alongside
intact or even superior systemizing (the drive to analyze or construct
systems).
Environmental exposures early in the 1st trimester of pregnancy that
have been linked to ASD in epidemiologic studies include thalidomide,
misoprostol, rubella infection, valproic acid, and the organophosphate
insecticide chlorpyrifos. Prenatal folic acid supplementation may
reduce the risk of ASD. There has been concern about vaccines as a
postnatal environmental cause for ASD. The focus has been on either
the measles-mumps-rubella vaccine or the thimerosal preservative
as a causative factor. All available data have not supported either
hypothesis.

Neuropathology Factors

The head circumference in ASD is normal or slightly smaller than


normal at birth until 2mo of age. Afterward, children with ASD show
an abnormally rapid increase in head circumference from 6-14mo of
age, increased brain volume in 2-4yr olds, increased volume of the
cerebellum, cerebrum, and amygdala, and marked abnormal growth in
the frontal, temporal, cerebellar, and limbic regions of the brain. Early,
accelerated brain growth during the first several years of life is followed
by abnormally slow or arrested growth, resulting in areas of underdeveloped and abnormal circuitry in parts of the brain. Areas of the brain
responsible for higher-order cognitive, language, emotional, and social
functions are most affected.

CLINICAL COURSE

ASD symptoms are typically recognized during the 2nd yr of life but
can been seen earlier than 12 mo if developmental delays are severe.
Initial symptoms most frequently involve delayed language accompanied by lack of social interest or odd play patterns. During the 2nd
yr, odd and repetitive behaviors and the absence of typical play
become more apparent. It is typical for parents to report that there
was no period of normal development or that there was a history of
unusual behaviors. Less commonly (in 20-40% of cases), a period of
apparently normal development is reported before a loss of skills. In
adolescence, a small number of individuals with ASD make marked
developmental gains; another subgroup will deteriorate (self-injury,
aggression).

DIFFERENTIAL DIAGNOSIS

ASD must be differentiated from communication disorders (especially


social communication disorder), intellectual disability (see Chapter
36), sensory impairments (especially deafness), reactive attachment

disorder, obsessive-compulsive and related disorders, anxiety disorders


(see Chapter 25) including selective mutism, schizophrenia (see
Chapter 31), stereotypic movement disorder (see Chapter 24.2),
attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome
(see Chapter 599).
Autistic-like behavior has been noted in many metabolic syndromic
and genetic disorders. These include adenylosuccinate lyase deficiency,
PKU, glucose-6-phosphatase deficiency, adenosine deaminase deficiency, succinic semialdehyde dehydrogenase deficiency, disorders of
creatine transport and metabolism, propionic acidemia, MELAS and
other mitochondrial disorders, Danan disease, tuberous sclerosia,
fragile X syndrome, Smith Lemli Opitz syndrome, myotonic dystrophy,
dystrophinopathies, Cohen and Myhre syndromes, muscle-eye-brain
disease, and various genetic microdeletions or duplications, including
deletion 22q11.2.
Developmental language disorders and intellectual disability have an
impact on socialization and may be mistaken for ASD. The distinction
is particularly difficult in preschool children. When an individual
shows impairment in social communication and social interactions but
without abnormal nonverbal communication or restricted, repetitive
patterns of behavior, a diagnosis of social communication disorder
should be considered. If there is no apparent discrepancy between the
level of social-communicative skills and other intellectual skills, a diagnosis of intellectual disability should be considered.
Children with reactive attachment disorder (typically occurring in
the face of emotional neglect; see Chapter 40) may exhibit deficits in
attachment and therefore inappropriate social responsivity, but these
usually improve substantially if adequate caretaking is provided.
Obsessive-compulsive disorder (see Chapter 25) has a later onset than
ASD, is not typically associated with social and communicative impairments, and is characterized by repetitive patterns of behavior that are
ego dystonic. Symptoms that characterize anxiety disorders, such as
excessive worry, the need for reassurance, the inability to relax, and
feelings of self-consciousness are also seen in ASD, particularly among
higher functioning individuals. However, the 2 conditions can be differentiated by the prominent social and communicative impairments
seen in ASD but not anxiety disorders, and the developed social insight
of children with anxiety disorders, which is not seen in ASD. Differentiating childhood schizophrenia from autism can be difficult, as both
are characterized by social impairments and odd patterns of thinking;
florid delusions and hallucinations are rarely seen in autism.
Motor stereotypies are among the diagnostic criteria for ASD, so an
additional diagnosis of stereotypic movement disorder should not
be given if the movements are better explained by ASD. However
when stereotypies cause self-injury and become a focus of treatment,
both diagnoses may be appropriate. Similarly, an additional diagnosis
of ADHD should only be given when attentional difficulties or hyperactivity exceed those typically observed in children of comparable
mental age.
During the regressive phase of Rett syndrome (ages 1-4yr), disruptive social interaction may be observed and affected children may meet
diagnostic criteria for ASD. After this phase, social communication
improves and an additional diagnosis of ASD should be considered
only if all criteria for ASD are met.

COMORBIDITIES

Given difficulties in communication (mutism) and cognitive impairment, issues of comorbidity in ASD can be quite complex. The process
of diagnostic overshadowing (the tendency to fail to diagnosis other
comorbid conditions when a more noticeable condition is present)
may occur. Most studies do show increased rates of anxiety and attentional disorders.
In most epidemiologically based samples of persons with autistic
disorder, approximately 50% exhibit severe or profound intellectual
disability, 35% exhibit mild to moderate intellectual disability, and the
remaining 20% have IQs in the normal range. Verbal skills are typically
more impaired than nonverbal skills. Intellectual impairment is not an
essential diagnostic feature of autism; it is necessary and important for
the diagnosis of intellectual disability to be made.

180 Part III Behavioral and Psychiatric Disorders


Neurologic comorbidities include epilepsy, sleep dysfunction, motor
delay, dyspraxia, incoordination, and gait disturbances.
A range of behavioral difficulties can be observed in ASD including
hyperactivity, obsessive compulsive phenomena, self-injury, aggression, stereotypies, tics, and affective symptoms. The issue of whether
these qualify as additional disorders is complex. Affective symptoms
are frequently observed and include lability, inappropriate affective
responses, anxiety, and depression. Impairments in emotion regulation
processes can lead to under- and overreactivity. Overt clinical depression is sometimes observed, and this may be particularly true for
adolescents. Case reports and case series suggest possible associations
with bipolar disorders and tic disorders. Attentional difficulties
(ADHD) are also frequent in autism, reflecting cognitive, language,
and social problems.

problems with independent living, employment, social relationships,


and mental health. Some children, especially those with communication abilities, can grow up to live self-sufficient lives in the community
with employment. Others remain dependent on their family or require
placement in facilities outside the home. Because early, intensive
therapy can improve language and social function, delayed diagnosis
can lead to a poorer outcome. A better prognosis is associated with
higher intelligence, functional speech, and less-bizarre symptoms and
behavior. The symptom profile for some children might change as they
grow older, and risk of seizures or self-injurious behavior becomes
more common. ASD is not a degenerative disorder and it is typical for
learning and compensation to continue throughout life.

SCREENING/CASE FINDING

All children should receive autism-specific screening at 18 and 24mo


of age, in addition to broad developmental screening at 9, 18, and
24mo (Fig. 30-1). In some instances screening may be relevant to older
children, such as those who are more intellectually able and whose

SEQUELAE

Most persons with ASD remain within the spectrum as adults, and
regardless of their intellectual functioning, continue to experience

1a:
Pediatric patient at
preventive care
visit

1b:
Extra visit for autismrelated concern,
ASD risk factor, or
other develomental/
behavioral concern

Legend
2:
Perform surveillance

 Start

Score 1 for each risk factor:


- Sibling with ASD
- Parental concern
- Other caregiver concern
- Pediatrician concern

Score  2

 Action/process
 Decision

3:

4:

What is the
score?

Is this an 18- or
24-month visit?

Score  0
Yes

Score  1

No

3a:
Is the patient at
least 18 months
old?

No

Yes

5a:

5b:

5c:

Evaluate socialcommunication
skills

Administer ASDspecific screening


tool

Administer ASDspecific screening


tool

6b:

6a:

Are the results


positive or
concerning?

Are the results


positive or
concerning?

No

7a:
1. Provide parental education
2. Schedule extra visit within 1
month
3. Re-enter algorithm at 1b

Yes

Yes

8:
1. Provide parental education
2. Simultaneously refer for:
a. Comprehensive ASD evaluation
b. Early intervention/early childhood
education services
c. Audiologic evaluation
3. Schedule follow-up visit
4. Re-enter algorithm at 1b

No

7b:
1. Schedule next
preventive visit
2. Re-enter algorithm at 1a

Figure 30-1 Surveillance and screening algorithm: autism spectrum disorders (ASDs). (From Plauche Johnson C, Myers SM, Council on Children
with Disabilities: Identification and evaluation of children with autism spectrum disorders, Pediatrics 120:11831215, 2007.)

Chapter 30 Autism Spectrum Disorder 181

1a:
Pediatric patient at
preventive care
visit

1a - Developmental concerns,
including those about social skill
deficits should be included as one
of several health topics addressed at
each pediatric preventive care visit
through the first 5 years of life.
(Go to step 2)

2:
Perform surveillance
Score 1 for each risk factor:
- Sibling with ASD
- Parental concern
- Other caregiver concern
- Pediatrician concern

1b:
Extra visit for autismrelated concern,
asd risk factor, or
other developmental/
behavioral concern

1b - At the parents request, or when a concern is


identified in a previous visit, a child may be scheduled
for a problem-targeted clinic visit because of concerns
about ASD. Parent concerns may be based on
observed behaviors, social or language deficits, issues
raised by other caregivers, or heightened anxiety
produced by ASD coverage in the media. (Go to step 2)

2 - Developmental surveillance is a flexible, longitudinal, continuous, and cumulative process whereby health care
professionals identify children who may have developmental problems. There are 5 components of
developmental surveillance: eliciting and attending to the parents concerns about their childs development,
documenting and maintaining a developmental history, making accurate observations of the child, identifying the
risk and protective factors, and maintaining an accurate record and documenting the process and findings. The
concerns of parents, other caregivers, and pediatricians all should be included in determining whether
surveillance suggests that the child may be at risk of an ASD. In addition, younger siblings of children with an
ASD should also be considered at risk, because they are 10 times more likely to develop symptoms of an ASD
than children without a sibling with an ASD. Scoring risk factors will help determine the next steps, (Go to step 3)

For more information on developmental surveillance, see Identifying Infants and Young Children With Developmental Disorders in the Medical Home: An Algorithm for
Developmental Surveillance and Screening (Pediatrics 2006; 118:405-420).

3a -

3 - Scoring risk factors:

3:
What is the
score?

If the child does not have a sibling with an ASD and there are no concerns
from the parents, other caregivers, or pediatrician: Score  0 (Go to step 4)

If the child has only 1 risk factor, either a sibling with ASD or the concern of
a parent, caregiver, or pediatrician: Score  1 (Go to step 3a)

If the child has 2 or more risk factors: Score  2 (Go to step 8)

3a:

Is the patient at
least 18 months
old?

If the childs age is 18


months, (Go to step 5a)

If the childs age is 18


months, (Go to step 5b)

4 - In the absence of established risk factors and parental/provider concerns (score  0), a level-1 ASD-specific tool should be
administered at the 18- and 24-month visits. (Go to step 5c) If this is not an 18- or 24-month visit, (Go to step 7b).

4:
Is this an 18-or
24-month visit?

5a:
Evaluate socialcommunication
skills

Note: In the AAP policy, Identifying Infants and Young Children With Developmental Disorders in the Medical Home: An Algorithm for Developmental
Surveillance and Screening, a general developmental screen is recommended at the 9-, 18-, and 24-or 30-month visits and an ASD screening is
recommended at the 18-month visit. This clinical report also recommends an ASD screening at the 24-month visit to identify children who may regress after
18 months of age.

5a - If the childs age is 18


months, the pediatrician should
use a tool that specifically
addresses the clinical
characteristics of ASDs, such
as those that target socialcommunication skills.
(Go to step 6a)

5b:
Administer ASDspecific screening
tool

5b - If the childs
age is 18 months,
the pediatrician
should use an
ASD-specific
screening tool.
(Go to step 6a)

5c:
Administer ASDspecific screening
tool

5c - For all children


ages 18 or 24 months,
(regardless of risk
factors), the pediatrician
should use an ASDspecific screening tool.
(Go to step 6b)

AAP-recommended strategies for using ASD screening tools: Autism: Caring for Children with Autism Spectrum Disorders: A Resource Toolkit for Clinicians (in press)*

6a:

Are the results


positive or
concerning?

6a - When the result of the screening is


negative, Go to step 7a
When the result of the screening is
positive, Go to step 8

6b:

Are the results


positive or
concerning?

6b - When the result of the ASD screening (at 18and 24-month visits) is negative, Go to step 7b
When the result of the ASD screening (at 18- and 24month visits) is positive, Go to step 8

7a - If the child demonstrates risk but has a negative screening result,


information about ASDs should be provided to parents. The
pediatrician should schedule an extra visit within 1 month to address
any residual ASD concerns or additional developmental/behavioral
concerns after a negative screening result. The child will then re-enter
the algorithm at 1b. A wait-and-see approach is discouraged. If the only risk factor is a sibling with
an ASD, the pediatrician should maintain a higher index of suspicion and address ASD symptoms at
each preventive care visit, but an early follow-up within 1 month is not necessary unless a parental
concern subsequently arises.
7a:
1. Provide parental education
2. Schedule extra visit within 1
month
3. Re-enter algorithm at 1b

8:
1. Provide parental education
2. Simultaneously refer for:
a. Comprehensive ASD evaluation
b. Early intervention/early childhood
education services
c. Audiologic evaluation
3. Schedule follow-up visit
4. Re-enter algorithm at 1b

7b - If this is not an
18- or 24-month
visit, or when the
result of the ASD
screening is
negative, the pediatrician can inform the
parents and schedule the next routine
preventive visit. The child will then re-enter the
algorithm at 1a.
7b:
1. Schedule next
preventive visit
2. Re-enter algorithm at 1a

8 - If the screening result is positive for possible ASD in step 6a or 6b, the pediatrician should provide peer reviewed
and/or consensus-developed ASD materials. Because a positive screening result does not determine a diagnosis of
ASD, the child should be referred for a comprehensive ASD evaluation, to early intervention/early childhood education
services (depending on childs age), and an audiologic evaluation. A categorical diagnosis is not needed to access
intervention services. These programs often provide evaluations and other services even before a medical evaluation
is complete. A referral to intervention services or school also is indicated when other developmental/behavioral
concerns exist, even though the ASD screening result is negative. The child should be scheduled for a follow-up visit
and will then re-enter the algorithm at 1b. All communication between the referral sources and the pediatrician should
be coordinated.

AAP information for parents about ASDs includes: Is Your One-Year-Old Communicating with You?* and Understanding Autism Spectrum Disorders.*

*Available at www.aap.org

Figure 30-1, contd

182 Part III Behavioral and Psychiatric Disorders


social disability is therefore more likely to be detected later. A number
of screening instruments for ASD have been developed that may be
helpful to the pediatric practitioner. For example, the Modified Checklist for Autism in Toddlers (M-CHAT) is a free online 23-item autism
screening tool designed to identify children 16-30mo of age who
should receive a more thorough assessment for possible early signs of
ASD or developmental delay (https://www.m-chat.org/index.php).

ASSESSMENT

If screening indicates ASD symptomatology, a thorough diagnostic


assessment should be performed to determine whether full criteria are
met. Multidisciplinary assessment is optimal in facilitating early diagnosis, treatment, and coordinated multiagency collaboration. Evaluations from various professionals, including a developmental pediatrician
or pediatric neurologist, medical geneticist, child and adolescent psychiatrist, speech-language pathologist, occupational or physical therapist, or medical social worker may be indicated. The Autism Diagnostic
Observation Schedule (ADOS), which is a semistructured interactive
examination by a professional trained in its administration, is the standard diagnostic tool. The use of such instruments supplements, but does
not replace, informed clinical judgment.
All children with ASD should have a medical assessment, which
typically includes a physical examination, a hearing screen, a Woods
lamp examination for signs of tuberous sclerosis (see Chapter 596.2),
and genetic testing, which should include chromosomal microarray
(CMA). In a community sample of children with ASD, diagnostic yield
0.57% for fragile X testing, and 24% for CMA. CMA is recommended
by medical geneticists as the standard of care for the initial evaluation
of children with ASD, but does not always detect fragile X or Rett
syndromes.
Unusual features in the child (dysmorphology, staring spells) should
prompt additional evaluations. The categories of potential organic etiologies includes infectious (encephalitis or meningitis), endocrinologic (hypothyroidism), metabolic (homocystinuria, phenylketonuria),
traumatic (head injury), toxic (fetal alcohol syndrome), or genetic
(chromosomal abnormality). Certain developmental disorders, most
notably Landau-Kleffner syndrome, should be ruled out (characterized
by a highly distinctive electroencephalogram abnormality and marked
aphasia). Neuroimaging, electroencephalography, and additional laboratory tests should be obtained when relevant, based on examination
or history (testing for the MeCP2 gene in females for possible Rett
disorder). Table 30-4 summarizes potential medical tests in the assessment of ASD.
Psychological assessments that clarify cognitive ability and adaptive
skills are indicated for treatment planning. Deficits in language and
socialization often make it difficult to obtain an accurate estimate of a
childs intellectual potential. Some children with ASD perform adequately on nonverbal tests, and those with developed speech can show
adequate intellectual capacity. Communication assessment, including
measures of both receptive and expressive vocabulary as well as language use (particularly social or pragmatic), is also helpful relative to
diagnosis and treatment planning. Occupational and physical therapy
evaluations may be needed to evaluate sensory and/or motor difficulties. Sleep is also an important variable to assess.

TREATMENT

The pediatric practitioner should aim to foster a long-term collaborative relationship with the family that will vary in intensity over time.
For young children, diagnosis and identification of treatment programs will generally be the major focus, whereas for school age children behavioral and medication issues will often become a priority.
Vocational training along with future self-sufficiency planning becomes
critical in adolescence and early adulthood. It is helpful to the family
for the pediatric practitioner to maintain an active role in long-term
treatment planning, providing family support, and navigating the
healthcare and educational systems.

Psychosocial Interventions

Structured behavioral, educational, and communication interventions


are effective for many children with ASD and are associated with better

Table 30-4 Medical and Genetic Evaluation of Children


with Autism Spectrum Disorder
Recommended evaluations
Careful physical examination to identify dysmorphic physical
features
Macrocephaly
Woods lamp examination for tuberous sclerosis
Formal audiologic evaluation
Lead test; repeat periodically in children with pica
Chromosomal microarray
Consider if results of above evaluation are normal and if
accompanying intellectual impairment
FISH test for region 15q11q13 to rule out duplications in PraderWilli/Angelman syndrome
Fluorescence in situ hybridization (FISH) test for telomeric
abnormalities
Test for mutations in MECP2 gene (Rett syndrome) in females
DNA testing for fragile X syndrome
Metabolic testing to consider based on clinical features (emesis,
hypotonia, lethargy, ataxia, coarse facial features of a storage
disease, multiple organs involved)
Fasting blood glucose
Plasma amino acids
Ammonia and lactate
Fatty acid profile, paroxysmal
Carnitine
Acylcarnitine, quantitative
Homocysteine
Urine amino acids
Urine organic acids
Urine purine/pyrimidines
Urine acylglycine, random
Plasma 7-dehydrocholesterol (Smith-Lemli-Opitz disease screening)
Medical testing to consider based on clinical features
Complete blood cell count
Liver enzymes
Biotinidase
Thyroxine, thyroid-stimulating hormone
Ceruloplasmin/serum copper
EEG if the following clinical features are noted
Clinically observable seizures
History of significant regression in social or communication
functioning
Adapted from Barbaresi WJ, Katusic SK, Voigt R. Autism: A review of the state
of the science for pediatric primary care clinicians, Arch Pediatr Adolesc Med
160:1169-1175, 2006.

outcomes. Several comprehensive treatment approaches are effective


for certain groups of children, although none of the approaches has
clearly emerged as superior.
Applied behavioral analysis (ABA) is a behavioral intervention that
is informed by basic and empirically supported learning principles. A
widely disseminated comprehensive ABA program is Early Intensive
Behavioral Intervention. Early Intensive Behavioral Intervention is
intensive and highly individualized with up to 40hr per week of oneto-one direct teaching, initially using discrete trials to teach simple
skills and progressing to more complex skills such as initiating verbal
behavior. ABA techniques have efficacy for specific problem behaviors
and to be effective when applied to academic tasks, adaptive living
skills, communication, social skills, and vocational skills.
Older children and adolescents with relatively higher intelligence,
but with poor social skills and psychiatric symptoms, can benefit from
more intensive behavioral or cognitive-behavioral therapy and/or supportive psychotherapy. The focus is on achieving social communication competence, emotional and behavioral regulation, and functional
adaptive skills necessary for independence.
Children with ASD need a structured educational approach with
explicit teaching. Effective programs typically involve planned, intensive, individualized intervention with an experienced, interdisciplinary

Chapter 30 Autism Spectrum Disorder 183


Table 30-5 Level of Evidence for Pharmacologic Treatment of Target Symptoms in Autism Spectrum Disorder
PRIMARY TARGET SYMPTOM(S)

LEVEL OF EVIDENCE

2-Agonist

CLASS
Clonidine
Guanfacine

AGENT

Hyperactivity
Hyperactivity

Insufficient
Insufficient

Antipsychotics

Aripiprazole
Haloperidol
Risperidone
Risperidone
Olanzapine

Irritability, hyperactivity, stereotypy


Behavioral symptoms
Irritability, hyperactivity
Repetitive behavior, stereotypy
Global functioning

Established
Established
Established
Preliminary
Insufficient

Mood stabilizers

Divalproex sodium/Valproic acid


Lamotrigine
Levetiracetam

Irritability, repetitive behavior


Irritability, social behavior
Irritability

Insufficient
Insufficient
Insufficient

Norepinephrine reuptake
inhibitors

Atomoxetine

Hyperactivity

Preliminary

Serotonin reuptake inhibitors

Citalopram
Fluoxetine
Clomipramine

Repetitive behavior
Repetitive behavior
Repetitive behavior, stereotypy,
irritability, hyperactivity

Insufficient
Insufficient
Insufficient

Stimulants

Methylphenidate

Hyperactivity

Promising

Miscellaneous

Amantadine
Naltrexone

Hyperactivity, irritability
Social behavior, communication,
Indiscriminant learning, SIB
Hyperactivity
Irritability, social withdrawal

Insufficient
Insufficient

Naltrexone
Pentoxifylline

Preliminary
Preliminary

Established, >2 strong studies or >4 adequate studies in separate settings; Insufficient, lack of research or mixed outcomes; Preliminary, >1 adequate study;
Promising, >2 adequate studies.
Adapted from Siegel M, Beaulieu AA. Psychotropic medications in child with autism spectrum disorders: A systematic review and synthesis for evidenced based
practice. J Autism Dev Disord 42(8):15921605, 2012.

team of providers, and family involvement to ensure generalization of


skills. Two structured educational models with demonstrated efficacy
include the Early Start Denver Model and the Treatment and Education
of Autism and related Communication handicapped Children (TEACCH)
program. The individualized educational plan (IEP) should reflect an
accurate assessment of the childs strengths and vulnerabilities with an
explicit description of services to be provided, goals and objectives, and
procedures for monitoring effectiveness. Development of an appropriate IEP is central in providing effective service to the child and family.
Communication is generally addressed in the childs IEP in coordination with the speech-language pathologist. Children who do not yet
use words can be helped through use of alternative communication
modalities such as sign language, electronic communication boards,
visual supports, picture exchange, and other forms of augmentative
communication. For individuals with fluent speech, the focus should
be on pragmatic (social) language skills training.
There is a lack of evidence for most other forms of psychosocial
intervention. Studies of sensory-oriented interventions, such as auditory integration training, sensory integration therapy, and touch
therapy/massage have contained methodologic flaws and have yet to
show replicable improvements. There is also limited evidence thus far
for what are usually termed developmental, social-pragmatic models
of intervention. Children with ASD are psychiatrically hospitalized at
substantially higher rates than the non-ASD population. The efficacy
of this level of care is unknown, although there is preliminary evidence
for the efficacy of hospital psychiatry units that specialize in this
population.

Pharmacotherapy

Pharmacologic interventions (Table 30-5) may increase the ability of


children with ASD to benefit from educational and other interventions
as well as to remain in less-restrictive environments through the management of challenging behavior. Common targets for pharmacologic
intervention include associated comorbid conditions (anxiety, depression) and problematic target symptoms (e.g., irritability, hyperactivity,
repetitive behavior, stereotypy, self-injurious behavior).

The FDA has approved risperidone (ages 5-16yr) and aripiprazole


(ages 6-17yr) for the treatment of irritability in ASD, as evidenced by
physical aggression, self-injury, and severe tantrum behavior. In youth
weighing < 20kg, the initial dose of risperidone is 0.25mg/day with a
target dose of 0.5mg/day, and maximum does of 3mg/day. In those
weighing 20kg, the initial dose of risperidone is 0.5mg/day with a
target dose of 1mg/day, and maximum dose of 3mg/day. For aripiprazole, the initial dose is 2mg/day with a target dose of 5-10mg/day,
and maximum dose of 15mg/day.
The atypical antipsychotic agents also reduce hyperactivity in ASD,
though stimulants and atomoxetine appear to be promising for hyperactivity. There is also evidence that repetitive behaviors and stereotypies in ASD may respond to the antipsychotics. Selective serotonin
reuptake inhibitors do not have evidence supporting their use for
repetitive behaviors or irritability in ASD; they may have efficacy for
the treatment of co-occurring depressive and anxiety disorders. The
doses of these latter medications would parallel clinical prescribing
practices for the specific target symptom (hyperactivity) and/or mental
disorders. There is insufficient evidence to support the use of mood
stabilizers.
Combining medication with parent training appears to be moderately more efficacious than medication alone for reducing serious
behavioral disturbance, and modestly more efficacious for adaptive
functioning. Individuals with ASD may be non-verbal, so response to
medication is often judged by caregiver report. While this may help
assess the effectiveness of the selected medication, it must be remembered that the overall goal of pharmacotherapy is to facilitate the childs
adjustment and engagement with behavioral, educational, and communication interventions.
Intranasal oxytocin (IO) is a novel approach to treating ASD. In
preliminary studies, IO leads to increased social interactions, better
speech comprehension, reduced repetitive behaviors, and functional
MRI evidence of improved social attunement. There is currently a large
clinical trial testing the efficacy of IO.
Bibliography is available at Expert Consult.

Chapter 30 Autism Spectrum Disorder 183.e1


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