1. Identification of Autism Spectrum Disorder in Young Children Nancy Roizen, MD Director, Division of Developmental/Behavioral Pediatrics and Psychology Rainbow Child Development Center Professor of Pediatrics Case Western Reserve University

2. Ages and areas of concern, consultations 1,2,3 Screening: false+ and false _ DSM criteria in < 3 year olds Retrospective (1st yr videos) and prospective studies (Ausibs) ADOS changes EI data and recommendations

3. Age When Parents First Concerned Age of child (yr)AutismAsperger (N=608)% (N=155)% <1 15.3%14.8% 1<237.2%20.0% 2<546.9%52.9% 5<100.5%10.3% 10<150.2%0.6% >150%1.3% (Howlin & Aspharian. Devel Med Child Neuro (1999) 41:834-839)

4. First Problems to Concern Parents ProblemAutismAsperger (N=614) (N=156) Language development43.6%25.6% Social development & play19.0%24.3% General behavior prob (including 12.5%22.4% Feeding) Motor and other DD (e.g. toileting)8.8%5.7% Medical problems (e.g. hearing)7.6%6.4% Routines & rituals3.4%6.4% Other (e.g. school)2.4%3.8% Professionals concerned2.3%5.1% (Howlin & Aspharian. Devel Med Child Neuro (1999) 41:834-839)

5. Action Taken when Parents Sought Diagnostic Consultation Consultation 1st 2nd 3rd Autism AspergerAutism AspergerAutism Asperger N=614 N=156 N=559 N=136 N=356 N=130 Mean age child 2.05 3.50 3.09 5.19 5.35 9.02 % given diagnosis 9.4 8.3 43.6 33.0 67.1 60.0 % referred on 53.9 47.4 27.7 18.3 14.5 13.1 % told not to worry 26.2 30.1 5.0 13.9 1.0 7.7 %problem recognize 8.8 12.1 16.1 22.1 8.5 6.2 but no action Other 1.1 1.8 6.9 12.5 8.7 13.0 (Howlin & Aspharian. Devel Med Child Neuro (1999) 41:834-839)

6. FACTOIDS -In 8 year old children 1 in 150 have ASD -12-16% of all children have developmental & behavioral disorders -39% of young children enrolled in Medicaid have developmental, behavioral, or social delay -<50% identified as having problems before starting school -Only 20% of physicians routinely use structured developmental screening test -20% of all visits to pediatricians office are for developmental or behavioral concerns

7. Suzie is four years old and referred by her pediatrician for language delays and concerns about her lack of eye contact and possible autism. In the last 2 years she has been evaluated by a pediatric neurologist and another developmental pediatrician. By history, she says nothing when she is outside her home.

8. The differential diagnosis of a child with language delay: Intellectual disability Autism spectrum disorder Selective mutism Hearing loss Expressive language delay Environmental deprivation Verbal dyspraxia/apraxia

9. The parents report that she speaks with her siblings and somewhat less so with her parents at home. With much cajoling and a slow moving presentation of questions with assistance from the parents, she answered several but not all questions at age level. Questionnaires indicated anxiety

10. A diagnosis of selective mutism is made because she speaks only in specific situations and by history and observation exhibits significant anxiety. She is referred to Dr. Cunningham our clinical psychologist who has a special interest in anxiety. Dr. Cunningham begins counseling and suggests that medication be added to the treatment regimen as progress is going slowly with counseling.

11. What will happen with our child? She is young. Hopefully, through counseling and medication, she will get on a better trajectory. She needs to be more confident and comfortable to speak at school and other out-of-home situations. She might have problems with repeated issues of anxiety. Dr. Cunningham might be working with her intermittently for years.

12. Emphasis on Early Diagnosis -Mounting evidence that developmental disruption is present before 3 yrs of age in children subsequently diagnosed with ASD -Research on neuroplasticity and intervention for ASDs indicates that early intervention is likely to optimize the outcome for children with ASDs -Intervention may minimize or possibly prevent some handicapping symptoms such as sequelae of self-imposed social deprivation.

13. Important and Exciting Happenings in the Nation, State, and County Studies on Early Identification Studies on Improving Sensitivity and Specificity

14. Funds to Increase the Screening, Identification, and Intervention for ASD Nationally : Combating Autism Act is infusing monies into LEND, MCHB D-B Fellows Developmental-Behavioral Fellowships State of Ohio: AAP John Duby, MD Autism Education Pilot Project Rainbow Child Development Center Rainbow: Pediatric Neurology, Developmental- Behavioral Peds, Child Psychiatry Autism Treatment Network

15. SCREENING CHAT screening twice (if positive) of 16,235 infants at 18 months of age -12 failed all key items measuring proto-declarative pointing, gaze monitoring, and pretend play -At 7 yr of age: 9 autism, 1 PDD, 1 language disorder, and 1 normal -22 children were medium risk as missed proto-declarative pointing -At 7 yr of age: 1 autism, 9 PDD, 7 language disorders, 2 developmental delay, 1 CP, 1 nl -50 cases with autism in screening population only 10 identified as medium or high risk. -44 with PDD only 10 in medium or high risk group (Baird et al., J Am Acad Child Adoles Psychiatry. (2000)39:694-702.)

16. PROBLEMS: FALSE POSITIVES AND NEGATIVES

17. DSM-IV Diagnostic Criteria for Autistic Disorder A.A total of six (or more) items from (1), (2), and (3), with at least two from (1) and one each from (2) and (3): (1) qualitative impairment in social interaction, as manifested by at least two of the following: (a) marked impairment in the use of multiple non-verbal behaviors, such as, eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction (b) failure to develop peer relationships appropriate to developmental level (c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest) (d) lack of social or emotional reciprocity

18. DSM-IV Diagnostic Criteria for Autistic Disorder (cont) (2) qualitative impairments in communication as manifested by at least one of the following: (a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication, such as, gesture or mime) (b) in individuals with adequate speech, marked impairment in the ability to initiate of sustain a conversation with others (c) stereotyped and repetitive use of language or idiosyncratic language (d) lack of varied, spontaneous, make-believe play or social imitative play appropriate to developmental level

19. DSM-IV Diagnostic Criteria for Autistic Disorder (cont) (3) restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following: (a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus (b) apparently inflexible adherence to specific, nonfunctional routines or rituals (c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements) (d) persistent preoccupation with parts of objects

20. DSM-IV Diagnostic Criteria for Autistic Disorder (cont) B. Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction (2) language as used in social communication (3) symbolic or imaginative play C. The disturbance is not better accounted for by Rett’s Disorder or Childhood Disintegrative Disorder

21. Autism Spectrum Disorder (ASD)=autistic disorder, Asperger disorder, and pervasive developmental disorder-not otherwise specified

22. Children Younger Than 3 Years of Age: Apply 4 of DSM-IV Criteria -Marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction -Lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g. by lack of showing, bringing, or pointing out objects of interest) -Lack of social and emotional reciprocity -Delay in or total lack of the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime) (Stone et al. J Child Psychol Psychiatry. (1999) 40:219-226)

23. EARLY SOCIAL SKILL DEFICITS Typical: Social development usually parallels overall general function (motor+adaptive+language+cognitive domains) in typically developing children and in those with developmental delays ASD: social skills and language more delayed or “out of sync” with motor, adaptive, and cognitive function (Johnson. Pediatrics in Review (2008) 29:86-96)

24. JOINT ATTENTION (JA): lack or delay specific to autism Definition: normal, spontaneously developing behavior that demonstrates child’s joy in sharing an object or event with another person Spontaneous: child looks back and forth between interesting object and caregiver to share interest Responding: child looks in direction indicated by the pointing of a caregiver and connects. Typically at 10-12 months Initiating: child points to object to establish a connection with another person. Typically at 14-16 months. Show: “show” or bring an object to parent as if to say, “Look at this.” Typically at 14 to 16 months

25. SOCIAL ORIENTING: Ability to orient to verbal stimuli specifically one’s own name Typically at 8-10 months consistently turn toward the speaker when their name is called. ASD: fail to orient to name but may respond to environmental sounds

26. PRETEND (SYMBOLIC) PLAY: Using pretend actions with objects Typical: simple pretend play at 16-18 months with use of miniature representative items, talk on phone, feed doll. ASD: often have little interest in toys, frequently preferring everyday items such as string, sticks, books or videos for carrying. May be content to play alone for hours. Play usually sensory-motor, ritualistic or constructive. May enjoy “roughhouse play” and show fleeting moment of social relatedness.

27. PRELANGUAGE ABNORMALITIES Typical: cooing or babbling by 6 months. Inflection by 10-12 months ASD: quiet and make few vocalizations. Atypical vocalization with hum or grunt. May be irritable and cry for long periods of time. May not wave bye or extend arms to be picked up. Do not have back and forth babbling conversations. Do not add inflection at 10-12 months.

28. ABSENT OR DELAYED SPEECH Differential diagnosis: Hearing loss Global developmental delays due to intellectual disability Lack of stimulating environment Expressive language delay Dyspraxia Selective mutism Autism

29. LANGUAGE REGRESSION: 25% to 30% with ASD appear to develop normally and regress ASD: regression usually between 15 to 24 months most frequently 18 to 21 months Differential diagnosis of loss of language skills: Rett syndrome Neurodegenerative disorders Landau-Kleffner syndrome with seizures is usually >3 yr.

30. ATYPICAL LANGUAGE -false impression of “advanced speech” but is echolalic, ritualistic, and not functional -immediate echolalia in typical but delayed in ASD and can be pervasive, enduring, and larger chunks of verbal material -ASD: obsessed with labeling colors, shapes, and numbers but unable to use in conversation -recite jingles and ABCs but unable to ask for a drink or follow a command -can have giant words (e.g. Whatisit?) and “pop- up” words that seem out of context and to have no communicative intent and then disappear.

31. RESTRICTIVE INTERESTS, STEREOTYPIES, AND REPETITIVE BEHAVIORS -Typical, form attachments to stuffed animal but ASD prefers hard items like pens or ropes with more robust attachment needing to hold during dinner, etc -Stereotypies with hand flapping, twirling, finger movements, toe walking, licking, and sniffing. -Repetitive behavioral such as lining things up and protesting violently when directed to a new activity

32. Retrospective Studies Involving Home Videos - Home videos of first birthdays comparing children later diagnosed with ASDs compared to typically developing children and non-ASD-related developmental delays - Children with ASDs exhibited: Less frequent responding to their name Less frequent looking at the faces of other individuals Less often using a pointing gesture to request or to share interest (Landa. Nature Clinical Practice Neurology. (2008) 4:138-147)

33. Development in Infants with ASD in Infant Siblings of Children with ASDs - 87 Infants tested at 6, 14, and 24 months from high risk (sibs) and low risk groups - 6 months: no stat diff between siblings and unaffected group - 14 months: ASD group signif worse on all scales except visual reception - 24 months: ASD performed signif worse in all domains - developmental trajectory of ASD group had unusual slowing in performance between 14 and 24 months of age in ASD (Landa & Garett-Mayer. J Child Psychol and Psychiatry (2006) 47:629-638)

34. Social & Communication Development in Infant/Toddler Siblings of Children with ASDs -N=107 AUsibs (59 boys and 48 girls); N=18 low-risk controls -used Communication and Symbolic Behavior Scales Developmental Profile (CSBS DP), Mullen Scales of Early Learning or Preschool Language Scale, and other measures -Dx on clinical judgment and ADOS

35. - Early Diagnosis Group=diagnosis at 14 month visit (n=16) - Late Diagnosis Group= diagnosis after 14 months visit (n=14) - Expected 5-8% but 26%. Possible sampling bias as parents (44% at 6 mo & 76% at 14 mo) reported concerns - AUsibs group (n=19) exhibited language and/or social delays (broader autism phenotype or BAP) but not ASD (Land et al. Arch Gen Psychiatry. (2007) 64:853-864)

36. Autism Diagnostic Observation Scale (ADOS) Standardized semi-structured observational play and activity assessment of the child Module chosen depending on the developmental and language level of the child Scoring includes cut-offs for autism and autism spectrum disorder (ASD) Module 1 for children with no speech of single word has several items Response to name Response to smile Response to joint attention Anticipation of social routine Birthday party and snack Coded for social interaction and communication domains.

38. ADOS: Revised algorithm for improved diagnostic validity Coded for Social affect and restricted, repetitive behavioral (RRB) Research demonstrated that repetitive behaviors observed during administration were of diagnostic significance (La Couteru. (2008). J Autism Dev Disord;38:362-372.)

39. IMPROVING SENSITIVITY AND SPECIFICITY

40. AUTISM OBSERVATION SCALE FOR INFANTS (AOSI) Infants 6-18 months; 18-item direct observational measure Visual tracking; Coordination of eye gaze and action Disengagement of attention Orientation to name; Eye contact; Reciprocal social smile Differential response to facial emotion Anticipatory social response; Social interest and shared affect Imitation; Social babbling Cuddliness; Soothability Transitions; Motor control Atypical motor behavior; Atypical sensory behavior Bryson et al. J Autism Dev Disord (2008) 38:731-38.

41. Early Intervention Preschool-aged Children with ASDs - positive responses to >20 hours/week - interventions that target wide range of skills - average IQ gain of 20 points with ABA based on operant conditioning with discrete skills taught by use masses trail conducted outside the natural context - more-naturalistic applications of ABA (Pivotal Response Training) have been shown effective for teaching important social and communication skills

42. -similar improvements in developmentally based interventions in which teaching often occurs within the natural context. -number of hours of speech-language therapy received between 2 and 4 years by children with ASDs is related to their development of spoken language -National Research Council recommended 25 h/wk of therapy-based engagement which can be delivered by therapists, family members and other caregivers (Landa. Nature Clinical Practice Neurology. (2008) 4:138- 147.)

43. SUMMARY Need early identification: screening and diagnosis Better standardized tools and clinical diagnosis Increased EI services and data