Autistic Spectrum Disorders, Nelsons

176 Part III ◆ Behavioral and Psychiatric Disorders

Chapter 30

Autism Spectrum DisorderGiuseppe J. Raviola, Michael L. Trieu, David R. DeMaso, and Heather J. Walter

The essential features of autism spectrum disorder (ASD) are persis-tent 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.

DESCRIPTIONSocial Communication and Interaction DeficitsAberrant development of social communication and impaired ability to engage in reciprocal social interactions are hallmark symptoms of ASD. Deficits in social–emotional reciprocity (the ability to engage with others and share thoughts and feelings) are evident early in chil-dren 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 <6 mo 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 expres-sions, 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 someone’s pointing or eye gaze is characteristic. In patients with fluent language, poorly integrated verbal and nonver-bal 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 inap-propriate 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. 50–51.

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 PatternsThe second core characteristic of ASD is restricted, repetitive patterns of behavior, interests, or activities. These include stereotyped move-ments (hand flapping, finger flicking), repetitive use of objects (spin-ning 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 (dis-tress 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 indif-ference 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 devel-opmental delay.

SeverityThe 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 FeaturesASD is specified as occurring with or without accompanying intel-lectual and language impairment, and associated with a known medical or genetic condition, environmental factor, or other neurodevelop-mental, 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 12 mo, absent single words by 16 mo, and absent 2-word purposeful phrases by 24 mo, 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 function-ing 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 afore-mentioned 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 dis-ability 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. Levetirace-tam also causes a reversible autistic regression syndrome.

EPIDEMIOLOGYThe Centers for Disease Control and Prevention estimates the preva-lence of ASD in the United States as 11.3/1,000 (prior estimated preva-lence 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 immi-grant populations.

ETIOLOGY/RISK FACTORSGenetic and Familial FactorsThere 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 (<26 wk 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


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.

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 words—for example, using fewer than

10 words by the age of 2 yr)• 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 3 yr

• Reduced and/or infrequent use of language for communication—for 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 people’s 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 age—may 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

like—for 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 adult’s hand on objects)• Reduced and poorly integrated gestures, facial expressions, body

orientation, eye contact (looking at people’s 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

to—may 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 play—for 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.


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 defi-ciency, 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 diag-nosis 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 impair-ments, 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 dif-ferentiated 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. Differ-entiating 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 hyper-activity exceed those typically observed in children of comparable mental age.

During the regressive phase of Rett syndrome (ages 1-4 yr), disrup-tive 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.

COMORBIDITIESGiven difficulties in communication (mutism) and cognitive impair-ment, 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 atten-tional 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.

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 associ-ated with multiple abnormalities of mitochondrial DNA.

Neurobiologic FactorsThe 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 signifi-cance. A role for dopamine is suggested given the problems with over-activity and stereotyped mannerisms and the positive response of such behaviors to antipsychotic medications.

Neuropsychological correlates of ASD include impairments in exec-utive 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 FactorsThe head circumference in ASD is normal or slightly smaller than normal at birth until 2 mo of age. Afterward, children with ASD show an abnormally rapid increase in head circumference from 6-14 mo of age, increased brain volume in 2-4 yr 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 underde-veloped 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 COURSEASD 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 accompa-nied 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 DIAGNOSISASD must be differentiated from communication disorders (especially social communication disorder), intellectual disability (see Chapter 36), sensory impairments (especially deafness), reactive attachment


problems with independent living, employment, social relationships, and mental health. Some children, especially those with communica-tion 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 FINDINGAll children should receive autism-specific screening at 18 and 24 mo of age, in addition to broad developmental screening at 9, 18, and 24 mo (Fig. 30-1). In some instances screening may be relevant to older children, such as those who are more intellectually able and whose

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, aggres-sion, 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 depres-sion 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.

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

1a: Pediatric patient at

preventive carevisit

1b: Extra visit for autism-

related concern,ASD risk factor, or

other develomental/behavioral concern

2:

3:

Perform surveillance

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

7a:1. Provide parental education2. Schedule extra visit within 1 month3. Re-enter algorithm at 1b

8:1. Provide parental education2. Simultaneously refer for: a. Comprehensive ASD evaluation b. Early intervention/early childhood education services c. Audiologic evaluation3. Schedule follow-up visit4. Re-enter algorithm at 1b

7b:1. Schedule next preventive visit2. Re-enter algorithm at 1a

What is thescore?Score � 2�

No

No

Yes

Yes

NoNo YesYes

Score � 0

� Start

� Action/process

� Decision

Legend

Score � 1

4:Is this an 18- or24-month visit?

5a:Evaluate social-communication

skills

6a:Are the results

positive orconcerning?

6b:Are the results


5b:Administer ASD-specific screening

tool

5c:Administer ASD-specific screening

tool

3a:Is the patient atleast 18 months

old?

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 120:1183–1215, 2007.)


1a - Developmental concerns,including those about social skilldeficits should be included as oneof several health topics addressed ateach pediatric preventive care visitthrough the first 5 years of life.(Go to step 2)

3 - Scoring risk factors:

• 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)

4 - In the absence of established risk factors and parental/provider concerns (score � 0), a level-1 ASD-specific tool should beadministered 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).

3a -

• If the child’s age is �18 months, (Go to step 5a)

• If the child’s age is �18 months, (Go to step 5b)

5b - If the child’sage is �18 months,the pediatricianshould use anASD-specificscreening tool.(Go to step 6a)

5c - For all childrenages 18 or 24 months,(regardless of riskfactors), the pediatricianshould use an ASD-specific screening tool.(Go to step 6b)

5a - If the child’s age is �18months, the pediatrician shoulduse a tool that specificallyaddresses the clinicalcharacteristics of ASDs, suchas those that target social-communication skills.(Go to step 6a)

7a - If the child demonstrates risk but has a negative screening result,information about ASDs should be provided to parents. Thepediatrician should schedule an extra visit within 1 month to addressany residual ASD concerns or additional developmental/behavioralconcerns 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 withan ASD, the pediatrician should maintain a higher index of suspicion and address ASD symptoms ateach preventive care visit, but an early follow-up within 1 month is not necessary unless a parentalconcern subsequently arises.

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

7b - If this is not an18- or 24-monthvisit, or when theresult of the ASDscreening is

negative, the pediatrician can inform theparents and schedule the next routinepreventive visit. The child will then re-enter thealgorithm at 1a.

6a - When the result of the screening isnegative, Go to step 7a

When the result of the screening ispositive, Go to step 8

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

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

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

1b - At the parents’ request, or when a concern isidentified in a previous visit, a child may be scheduledfor a “problem-targeted” clinic visit because of concernsabout ASD. Parent concerns may be based onobserved behaviors, social or language deficits, issuesraised by other caregivers, or heightened anxietyproduced by ASD coverage in the media. (Go to step 2)

1a: Pediatric patient at

preventive carevisit

1b: Extra visit for autism-

related concern,asd risk factor, or

other developmental/behavioral concern

2:

3:

Perform surveillance

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

7a:1. Provide parental education2. Schedule extra visit within 1 month3. Re-enter algorithm at 1b

8:1. Provide parental education2. Simultaneously refer for: a. Comprehensive ASD evaluation b. Early intervention/early childhood education services c. Audiologic evaluation3. Schedule follow-up visit4. Re-enter algorithm at 1b

7b:1. Schedule next preventive visit2. Re-enter algorithm at 1a

What is thescore?

4:Is this an 18-or24-month visit?

5a:Evaluate social-communication

skills

6a:Are the results


6b:Are the results


5b:Administer ASD-specific screening

tool

5c:Administer ASD-specific screening

tool

Note: In the AAP policy, “Identifying Infants and Young Children With Developmental Disorders in the Medical Home: An Algorithm for DevelopmentalSurveillance and Screening”, a general developmental screen is recommended at the 9-, 18-, and 24-or 30-month visits and an ASD screening isrecommended at the 18-month visit. This clinical report also recommends an ASD screening at the 24-month visit to identify children who may regress after18 months of age.

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

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

3a:Is the patient atleast 18 months

old?

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

Figure 30-1, cont’d


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 Check-list for Autism in Toddlers (M-CHAT) is a free online 23-item autism screening tool designed to identify children 16-30 mo 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).

ASSESSMENTIf 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 diag-nosis, treatment, and coordinated multiagency collaboration. Evalua-tions from various professionals, including a developmental pediatrician or pediatric neurologist, medical geneticist, child and adolescent psy-chiatrist, speech-language pathologist, occupational or physical thera-pist, 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 stan-dard 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 Wood’s 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 eti-ologies includes infectious (encephalitis or meningitis), endocrino-logic (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 labo-ratory 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 assess-ment 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 child’s intellectual potential. Some children with ASD perform ade-quately 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 lan-guage 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 difficul-ties. Sleep is also an important variable to assess.

TREATMENTThe pediatric practitioner should aim to foster a long-term collabora-tive relationship with the family that will vary in intensity over time. For young children, diagnosis and identification of treatment pro-grams will generally be the major focus, whereas for school age chil-dren 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 InterventionsStructured 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 evaluationsCareful physical examination to identify dysmorphic physical

featuresMacrocephalyWood’s lamp examination for tuberous sclerosisFormal audiologic evaluationLead test; repeat periodically in children with picaChromosomal microarray

Consider if results of above evaluation are normal and if accompanying intellectual impairment

FISH test for region 15q11q13 to rule out duplications in Prader-Willi/Angelman syndrome

Fluorescence in situ hybridization (FISH) test for telomeric abnormalities

Test for mutations in MECP2 gene (Rett syndrome) in femalesDNA 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 glucosePlasma amino acidsAmmonia and lactateFatty acid profile, paroxysmalCarnitineAcylcarnitine, quantitativeHomocysteineUrine amino acidsUrine organic acidsUrine purine/pyrimidinesUrine acylglycine, randomPlasma 7-dehydrocholesterol (Smith-Lemli-Opitz disease screening)

Medical testing to consider based on clinical featuresComplete blood cell countLiver enzymesBiotinidaseThyroxine, thyroid-stimulating hormoneCeruloplasmin/serum copper

EEG if the following clinical features are notedClinically observable seizuresHistory 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 40 hr per week of one-to-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 sup-portive psychotherapy. The focus is on achieving social communica-tion 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, inten-sive, individualized intervention with an experienced, interdisciplinary

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The FDA has approved risperidone (ages 5-16 yr) and aripiprazole (ages 6-17 yr) for the treatment of irritability in ASD, as evidenced by physical aggression, self-injury, and severe tantrum behavior. In youth weighing < 20 kg, the initial dose of risperidone is 0.25 mg/day with a target dose of 0.5 mg/day, and maximum does of 3 mg/day. In those weighing ≥ 20 kg, the initial dose of risperidone is 0.5 mg/day with a target dose of 1 mg/day, and maximum dose of 3 mg/day. For aripip-razole, the initial dose is 2 mg/day with a target dose of 5-10 mg/day, and maximum dose of 15 mg/day.

The atypical antipsychotic agents also reduce hyperactivity in ASD, though stimulants and atomoxetine appear to be promising for hyper-activity. There is also evidence that repetitive behaviors and stereoty-pies 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 moder-ately 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 remem-bered that the overall goal of pharmacotherapy is to facilitate the child’s adjustment and engagement with behavioral, educational, and com-munication 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.

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 child’s strengths and vulnerabilities with an explicit description of services to be provided, goals and objectives, and procedures for monitoring effectiveness. Development of an appropri-ate IEP is central in providing effective service to the child and family.

Communication is generally addressed in the child’s IEP in coordi-nation 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 audi-tory 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.

PharmacotherapyPharmacologic 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 man-agement of challenging behavior. Common targets for pharmacologic intervention include associated comorbid conditions (anxiety, depres-sion) and problematic target symptoms (e.g., irritability, hyperactivity, repetitive behavior, stereotypy, self-injurious behavior).

Table 30-5 Level of Evidence for Pharmacologic Treatment of Target Symptoms in Autism Spectrum Disorder

CLASS AGENT PRIMARY TARGET SYMPTOM(S) LEVEL OF EVIDENCE

α2-Agonist Clonidine Hyperactivity InsufficientGuanfacine Hyperactivity Insufficient

Antipsychotics Aripiprazole Irritability, hyperactivity, stereotypy EstablishedHaloperidol Behavioral symptoms EstablishedRisperidone Irritability, hyperactivity EstablishedRisperidone Repetitive behavior, stereotypy PreliminaryOlanzapine Global functioning Insufficient

Mood stabilizers Divalproex sodium/Valproic acid Irritability, repetitive behavior InsufficientLamotrigine Irritability, social behavior InsufficientLevetiracetam Irritability Insufficient

Norepinephrine reuptake inhibitors

Atomoxetine Hyperactivity Preliminary

Serotonin reuptake inhibitors Citalopram Repetitive behavior InsufficientFluoxetine Repetitive behavior InsufficientClomipramine Repetitive behavior, stereotypy,

irritability, hyperactivityInsufficient

Stimulants Methylphenidate Hyperactivity Promising

Miscellaneous Amantadine Hyperactivity, irritability InsufficientNaltrexone Social behavior, communication,

Indiscriminant learning, SIBInsufficient

Naltrexone Hyperactivity PreliminaryPentoxifylline Irritability, social withdrawal 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):1592–1605, 2012.

Chapter 30 ◆ Autism Spectrum Disorder 183.e1

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