Ozonoff_Jan2012

Early Signs of Autism: Rethinking Onset

Pamela J Turbeville Speaker Series Frances McClelland Institute

University of Arizona

Sally Ozonoff, Ph.D. Professor and Vice Chair

MIND Institute, UC Davis

January 27, 2012

Outline

  Autism signs in early childhood   Symptom onset patterns   Infant sibling study

  Recurrence risk   Clinical implications

Earlier Identification of ASD

  Mean age of autism diagnosis = 34 – 61 months   Mean age of first parental concern = 18 – 19 months

  30–50% report concerns before 1st birthday

Earlier identification Earlier intervention

Symptom Onset Patterns

  By DSM-IV definition, symptoms present by 36 months

  Patterns of symptom emergence   Early Onset: Differences in development in first

year of life   Regression: Achievement of early milestones,

followed by loss of skills   [Plateau: Typical early development followed by

failure to progress, gain new skills]

Signs of Autism in the First Years of Life

  Reduced attention to face and eyes of others   Limited response to name   Little showing and sharing of attention

  Delayed development of pointing

  Limited shared affect

Baranek, 1999; Lord, 1995; Osterling et al., 2002; Stone et al., 1994; Wetherby et al., 2004

Regression

  Average age of onset 19 – 21 months   25 – 40% of children with ASD   Gradual course   Both loss of acquired skills (language, social)

and onset of stereotypies and other symptoms of autism   Motor, self-help, and other losses rare

Goldberg et al., 2003; Ozonoff et al., 2005; Rogers, 2004; Shinnar et al., 2001; Werner & Dawson, 2005

Measurement of Symptom Onset

  Retrospective   Parent report   Home video review

  Prospective   Longitudinal measurement of social and

communication development

Prospective Study Designs

?

High Risk Low Risk

?

Earliest signs Onset patterns Stability of diagnosis Earliest intervention

UC Davis – UCLA Infant Sibling Study

  Goals 1)  How early can we identify autism in babies? 2)  What are the earliest signs of autism? 3)  Are siblings of children with autism at higher risk

for developing autism? 4)  Do other developmental problems occur in infant

siblings?

PhaseI2003‐2008 N=350

36 Months

24 Months

18 Months

12 Months

6 Months


outcomeassessment

PhaseI2003‐2008 N=350

PhaseII 2008‐2013 N=300

36 Months

24 Months

18 Months

12 Months

6 Months

School Age

36 Months

24 Months

18 Months

12 Months

9 Months

6 Months

15 Months


Sample Characteristics

High-Risk Infants (n=223)

Low-Risk Infants (n=124)

Gender (% Male) 52.0% 54.0%

Mean gestational age in weeks (sd) 38.9 (1.7) 39.1 (1.8)

% Hispanic ethnicity 20.2% 11.1%

% Racial minority 27.2% 18.8%

Family income level a (sd) 4.0 (1.6) 4.3 (1.6)

a 6-point scale, with 1 = less than $25,000 and 6 = more than $125,000 (4 = $75,000 - $99,999)

Measures

Communication ESCS, Mullen, MacArthur CDI, Language Use Inventory, speech perception

Social-Emotional Peek-a-boo, imitation, empathy, parent-child play, response to name

Face Processing Eye gaze during still face paradigm

Autism Symptoms AOSI, ADOS, ADI, SRS

Other Cognitive (Mullen), adaptive (Vineland), motor, head circumference, visual processing, smooth pursuit

Measures

  Response to name   Social communication   Object exploration

  Objects that afford both typical and unusual usage   Typical: mouth, bang, shake, throw   Atypical: roll, spin, rotate, prolonged visual

exploration

Object Exploration Task (12 Months)

***

**

*

Emotional Responsiveness

Low risk 12-month-old 12-month-olds later diagnosed with ASD

Gaze and Affect during Social Interaction and Still-Face

  6-month-old low risk infant   6-month-old high risk infant   Same high risk infant at 12 months

Distribution of Eye Ratio by Sibling Group (Merin et al 2007)

Does Focus on Mouth Predict Autism? (Young et al, 2009)

4 participants autism or ASD

SE = 0

SP = .769

Group Differences: High v Low Risk Infants

6 m 12 m 18 m 24 m 36 m

Mullen language

MCDI vocabulary

Vocalization freq

Empathy

ESCS joint attention Response to name

Face processing

Imitation

Eye contact frequency

Examiner social ratings

Repetitive object use

Measurement of Onset Patterns

  Retrospective   Parent report   Home video review

  Prospective   Longitudinal measurement of social and

communication development

Worsening Trajectory

Prospective Tracking of Symptoms

Mean age of diagnosis = 24.6 months

Symptom Onset

Computed 95% CI around change from one visit to the next for TD sample

Ozonoff et al., 2010, JAACAP

Symptom Onset

19/22 children with ASD demonstrated declining trajectory, falling outside typical 95% CI

Ozonoff et al., 2010, JAACAP

Retrospective v. Prospective Measurement

  Parents did not observe the declines in social-communication behavior that were documented prospectively

  Only 4 of 19 parents reported a regression on the ADI-R

A Continuum of Regression?

birth 36 months LOSS OF SKILLS

Occurs so early that symptoms appear to have always been present

Occurs so late that change appears dramatic and is easier to recognize


  Goals 1)  How early can we identify autism in babies? 2)  What are the earliest signs of autism? 3)  Are siblings of children with autism at higher risk

for developing autism? 4)  Do other developmental problems occur in infant

siblings?

Recurrence Risk

  Previous estimates (1980’s & 90’s)   3 – 10%   Significantly higher than population rate

  Earlier studies based on rate of multiplex families   Does not account for stoppage phenomenon

Baby Siblings Research Consortium (BSRC)   Sample

  664 high risk [338 low risk infants]   12 sites: UC Davis, UCLA, UCSD, Kennedy Krieger

Institute, University of Miami, Washington University-St. Louis, University of Alberta, University of Toronto, Dalhousie University, McMaster University

  36-month outcome   ADOS and expert clinician diagnosis

Ozonoff et al. (2011). Recurrence risk for ASD: A Baby Siblings Research Consortium study. Pediatrics, 128(3), e488-e495

Baby Siblings Research Consortium (BSRC)

  Largest sample to date   Geographically diverse   Later-born siblings   Expert gold standard assessments   Prospective

  2/3 enrolled before 6 months of age


Results

  Prevalence of ASD significantly higher than previous estimates

  18.7% of high-risk siblings developed ASD   Even higher recurrence rates in

  Male infants   Multiplex families


ASD Outcomes by Risk Group and Infant Gender

. Ozonoff et al. (2011). Recurrence risk for ASD: A Baby Siblings Research Consortium study. Pediatrics, 128(3), e488-e495

ASD Outcomes by Multiplex Status and Infant Gender


Results

  Recurrence not predicted by   Sex of proband   Functioning level of proband   Age of infant at enrollment   Birth order   Parent age   Race or ethnicity   SES


ASD Other Developmental Concerns Typical Development

Other 36 Month Outcomes

13%

30%

Speech delay

Social delays

Global delays

Hyperactivity

Anxiety

Implications

  ASD in the family is a significant risk factor   Increases overall risk 20 times higher than general

population risk   Infants must be much more closely monitored

  Additional surveillance and screening   Earliest diagnosis Earliest intervention


Major Conclusions

Are siblings of children with autism at higher risk for autism?

YES, especially males and those with more than one affected sibling

Do other developmental problems occur in infant siblings?

YES, especially language delays

How early are signs first evident? 9 – 12 months

What are the earliest signs? Poor response to name, decreasing eye contact, smiling, social interest

Conclusions, continued

Autism emerges over time

Signs of autism not “present at birth” in many children

Losing skills may be much more common than previously thought

Regression often subtle, gradual, and difficult to observe in real time and capture via parent report

Clinical Implications

Infants with risk signs should be offered interventions for symptoms, not wait for definitive diagnosis Development of treatments for infants is an urgent priority Continued search for markers that identify risk BEFORE the onset of behavioral signs Screening for autism needs to be done multiple times in first several years of life

Red Flags for Autism in Infancy

  Before 6 months Looking at faces Smiling at others Cooing

  12 – 18 months Pointing and showing Using single words Using gestures Imitating Interested in peers

Babies should be referred who are not…

  6 – 12 months Responding to name Babbling Playing social games Displaying bright affect

AAP Practice Recommendations (2007)

  Primary care providers should …   Be aware of early signs   Perform developmental surveillance

and elicit parent concerns at every visit   Administer standardized screening

measure if indicated   Perform formal screens for autism at

18 and 24 months for all children

Screening Tools   Autism-specific screeners

  Infant-Toddler Checklist (ITC)   6 – 24 months   http://firstwords.fsu.edu/pdf/checklist.pdf

  Modified Checklist for Autism in Toddlers (M-CHAT)   16 – 30 months   https://www.m-chat.org

Early Diagnostic Stability Study Sample Stability Cox et al. 1999 T1: 20-42 m

T2: 7 years ASD: 100%

Stone et al.1999 T1: mean 30 m T2: 42-48 m

Autism: 100% ASD: 33%

Lord et al. 2006 T1: mean 30 m T2: 7 years

ASD: 90%

Chawarska et al. 2007 T1: mean 21m T2: ~1.5 yrs later

ASD: 100%

Stone et al. 2007 T1: 2 y T2: 4 y

ASD: 63%

Kleinman et al. 2008 T1: 16-35 m T2: 42-82 m

ASD: 81%

Working with Families

  Acknowledge, do not dismiss, parent concerns   Have open and honest discussions

  Be willing to express uncertainty   Acknowledge range of outcomes, imperfection of prediction

of severity   Discuss repercussions of false negatives and false

positives   Families will differ in their values

  Provide parenting strategies and practical advice

Caronna et al, 2007

Resources

  Does My Child Have Autism? A Parent’s Guide to Early Detection and Intervention by Stone & DiGeronimo (2006)

  http://www.aap.org   http://www.autismspeaks.org

  First 100 Days kit   Learn the Signs ad campaign   Video Glossary

  http://www.firstsigns.org   Free screening kit for pediatricians

Many Thanks To

  Participating families   Funding from

  National Institute of Mental Health   R01 MH068398 [Ozonoff, UC Davis]   U54 MH068172 [Sigman, UCLA]

  Autism Speaks   M.I.N.D. Institute

  Infant Sibling Team

www.mindinstitute.org

Ozonoff_Jan2012

Documents

months school age

early signs of autism

earliest signs of autism

age of autism diagnosis

outline autism signs

symptoms of autism motor

new skills signs of

onset of stereotypies