1. Autism Spectrum Disorders (ASDs): Perspectives on Surveillance, Research, and Early Identification. Marshalyn Yeargin-Allsopp, M.D. National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention (CDC) Atlanta, GA The First International Autism Summit Renaissance Cleveland Hotel Cleveland Ohio, October 10-12, 2008

2. Overview  Surveillance: How common is Autism?  Current Prevalence  Trends over time  CDC’s Role  Research: What are potential “Causes”  Biology  Genetics  Gene/Environment Interaction  Studies to Measure Impact SEED NCS  Identification: Learn the Signs  Implementing AAP Recommendations  Role of Early Intervention  Treatments: Act Early  Proposed “cures”  Behavioral Intervention

3. What is Autism?

4. Autism is…  Developmental disability  not present at birth  Different brain structure  complex genetic interaction + ??? Complex disorder  many areas affected Wide range of impairment  mild to severe across areas

5. Autism Spectrum Disorders (ASD) Pervasive Developmental Disorders (PDD) PDD = an “umbrella category” Autism Atypical Autism (PDD-NOS) Asperger’s Disorder Childhood Disintegrative Disorder Rett Syndrome

6. Pervasive Developmental Disorders (APA, 1994) Autism: Communication, Social, Behaviors/Interests PDD-NOS: Atypical autism Asperger’s: Social, Behaviors/Interests, no significant language or cognitive delay Rett: females, deceleration, hand use CDD: normal development & significant loss of skills

7. Surveillance: How common is Autism?

9. Autism prevalence trend studies  France – stable  Sweden – increase in rates of autism and severe MR or normal intelligence  England, Wales – increase attributed to improved recognition with largest increases in ASD (not autistic disorder)  Australia – increase in “referrals”  USA – increase in “research-identified” ASD

10. Challenges of Interpreting ASD Prevalence Trends Studies from different populations Different methods between studies Changing diagnostic criteria Expansion of autism to a “spectrum” of disorders Increasing recognition that ASDs co-occur with other disorders Changes in level of awareness and use of diagnosis over time

11. What is CDC’s Role in Autism?

12. 1968: Surveillance for Birth Defects 1979-80: Request for presentation of data on ID and CP 1981: EIS Officer assigned to Birth Defects Branch to study DDs 1981-83: Pilot study of MR in DeKalb County, GA CDC’s Efforts in DD Surveillance: The Early Years

13. Objectives: Develop methods for population-based surveillance of DDs and estimate prevalence rates of intellectual disability, cerebral palsy, visual impairment, hearing loss, and epilepsy. 1984-1990: Metropolitan Atlanta Developmental Disabilities Study (MADDS)

14. Who: Ten-year old children in 1985, 1986, 1987 Where: Clayton, Cobb, DeKalb, Fulton, and Gwinnett Developmental Disabilities Monitored:Cerebral Palsy, Mental Retardation, Hearing Impairment, Visual Impairment, and Epilepsy Methods:Population-based, active record review at multiple sources MADDS Study Population and Methods

15. Mental Retardation Total 1074 Cerebral Palsy Visual Impairment Hearing Impairment 204 61 1001.1 0.7 2.3 12.03.1-43.6 N RatePrevious Studies Estimates from 2.0-3.0 0.3-0.6 0.6-2.3 Epilepsy 538 6.04.0-9.0 MADDS: Prevalence of Five Developmental Disabilities Per 1000 Ten-Year-Old Children, 1985-1987

17. Brick Township Prevalence Investigation  Study Characteristics:  Children 3-10 years of age (N=8,896)  Residence in 1998 was Brick Township  Case Identification:  Schools, special programs  Physician/other diagnosticians  Parent groups/self referrals  Case Verification  Special examination- diagnosis of autism: ADOS  Review of available records

18. Brick Township, New Jersey: Prevalence of ASD, 3-10 Year Old Children Prevalence 95% CI Rate per 1,000 __________________________________________ Autism Spectrum Disorders60/8,896 5.1 – 8.7 6.7 Autistic Disorder36/8,896 2.8 – 5.6 4.0 Bertrand J et al. (2001) Prevalence of Autism in a United States Population: The Brick Township, New Jersey, Investigation. Pediatrics, 108(5): 1155-1161.

19. 1991-Present: Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) Expanded upon MADDS methods Five counties Active record review at multiple sources 1991-1994: 3-10 year olds for ID, CP, HL, and VI 1996: 8-year-olds for ID, CP, HL, VI Autism added, 3-10 year olds 2000, 2002, 2004, 2006, 2008-ongoing: 8-year-olds for ASD, ID, CP, HL, and VI

20. MADDSP Data Sources  GA Department of Education (ED)  Metro Atlanta school systems – special education  State schools  Regional psychoeducational programs  GA Department of Human Resources (DHR)  Division of Public Health/CMS  Division of MH/DD/AD  Pediatric hospitals and associated clinics  Diagnostic centers  Other clinical providers

21. Washington Montana Oregon Nevada California Utah Arizona New Mexico Colorado Idaho Wyoming North Dakota South Dakota Minnesota Iowa Nebraska Kansas Texas Florida Mississippi Louisiana Alabama Georgia South Carolina North Carolina Virginia Maine New York Michigan Wisconsin Oklahoma Missouri Arkansas Tennessee Kentucky Illinois Indiana Michigan Ohio West Virginia DC Maryland Delaware New Jersey Vermont Rhode Island Connecticut New Hampshire Massachusetts Alaska Hawaii Pennsylvania U.S. Virgin Islands Puerto Rico Guam CDC 11 ADDM Sites 2006-2010 (10+CDC) 16 ADDM Sites 2001-2006 (15 +CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network +

22. Goals: Accurate and comparable population-based estimates of the prevalence of Autism Spectrum Disorder (ASD) in selected regions of U.S. Describe the characteristics of children with Autism Examine trends in prevalence

23. ADDM 2002 Study Year: 4 out of 14 sites with Health Source Access Only SiteArea8-year-olds in Population in 2002 1. Alabama32 counties35,472 2. Missouri5 counties28,049 3. Pennsylvania1 county21,061 4. Wisconsin10 counties35,126 2002 sites continued…

24. ADDM 2002 Study Year: 10 out of 14 sites with Health and Education Source Access SiteArea8-year-olds in Population in 2002 5. ArkansasStatewide36,472 6. Arizona1 county45,113 7. Colorado2 counties11,020 8. Georgia5 counties44,299 9. Maryland5 counties29,722 10. New Jersey4 counties29,748 11. North Carolina10 counties20,725 12. South Carolina23 counties23,191 13. Utah3 counties26,108 14. West VirginiaStatewide21,472 14 site total407,578 Approximately 10% of US population of 8-year-olds

25. ADDM 2002 ASD Prevalence Results The overall ASD prevalence per 1,000 8-year-olds ranged from 3.3 (AL) to 10.6 (NJ). 12 of 14 sites with total ASD prevalence between 5.2 and 7.6 per 1,000 children. The weighted average prevalence was 6.6 per 1,000 across all sites.  The weighted average was 5.1 for sites with access to health data only and 7.2 for health + education

26. Prevalence Conclusions Results from the largest US multi-site collaboration to monitor ASDs underscore that ASDs are conditions of urgent public health concern. For the majority of communities represented, ASD prevalence ranged from 5.2-7.6 per 1000 children Some variation  ASD prevalence significantly lower in 1 site (AL) and higher in 1 site (NJ).  Average of 1 in 150 children (range from about 1 in 100 to 1 in 300) How many children in the U.S. have an ASD? How many children in the U.S. have an ASD?  Estimated: 560,000 children between 0-21 years

27. Research: Exploring suspected “causes” of autism…

28. Dramatic secular trend in ASD prevalence shown in administrative and research data Source: DDS. Autism Spectrum Disorders – Changes in the California Caseload. An update: 1999 through 2002; April 2003 Real Risk Change Changing Diagnostic Tendency vs. EVIDENCE? Persons with Autism in California Department of Developmental Services Client Database by Year Lingering uncertainty around causes of increasing secular trend in autism prevalence Slide courtesy of is Craig Newschaffer

29. Etiology Support for biological mechanism: MR in 70-90% (older studies) EEG abnormalities Abnormalities of brain  amygdala  hippocampus  septum  mammillary bodies  cerebellum Increased head circumference Large, heavy brain at autopsy Abnormalities from chromosomal studies e.g., duplication/deletion Evidence that abnormality occurs 20- 24 days postconception

30. Etiology Evidence that Autism is a genetic disorder: Recurrence rate in families 75-fold increased risk in siblings 10-40% increased prevalence of ASD and related disorders in families Twin Studies 75-90% concordance in monozygotic twins 5-10% concordance in same-sex dizygotic twins Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May; 30(3): 405-16.

31. Can lead to overestimation of heritability Hampers the ability of genetic linkage and association studies to find genes Gene- environment interaction is one potential source of complexity Slide courtesy of is Craig Newschaffer

32. Measuring the Impact  CDC’s Study to Explore Early Development  National Children’s Study

33. Washington Montana Oregon Nevada California Utah Arizona New Mexico Colorado Idaho Wyoming North Dakota South Dakota Minnesota Iowa Nebraska Kansas Texas Florida Mississippi Louisiana Alabama Georgia South Carolina North Carolina Virginia Maine New York Michigan Wisconsin Oklahoma Missouri Arkansas Tennessee Kentucky Illinois Indiana Michigan Ohio West Virginia DC Maryland Delaware New Jersey Vermont Rhode Island Connecticut New Hampshire Massachusetts Alaska Hawaii Pennsylvania U.S. Virgin Islands Puerto Rico Guam CADDRE grantees, including Data Coordinating Center CDC, 6 th CADDRE site

34. Main research areas  ASD phenotypic variation  Subgrouping for etiologic analysis  Infection and immune function, including autoimmunity  Reproductive and hormonal features  Gastrointestinal features  Genetic features  Sociodemographic features Study to Explore Early Development (SEED)

35. The National Children’s Study 100,000 children across the United States Followed from before birth until age 21 Looking at environmental influences With the goal of improving the health and well-being of children.

36. Families who participate in the National Children’s Study will come from 105 Study locations (counties or groups of counties) across the United States. OHIO: A -Cuyahoga County, OH B -Lorain County, OH ( To become active 2008-2010) The National Children’s Study: Locations

37. Identification: Learn the Signs

38. Time Magazine; May 6, 2002

39. www.cdc.gov/actearly Learn the Signs. Act Early.

40. AAP Algorithm for Developmental Surveillance and Screening – July 2006

41. The AAP Clinical Reports recommend: Conduct ASD surveillance at all preventative well child visits Screen all children at 18 and 24 months and when surveillance reveals a concern for ASD Increased vigilance in younger siblings with a 10x increased risk Strategies to care for children with ASD within a Medical Home

42. Introduction Identification  Algorithm  Surveillance tools  Screening tools Referral  Forms, sample letters and coding information Physician Fact Sheets  Strategies for management of common co-morbidities Family Handouts  Tips for parents

43. Treatment of Autism: Act Early

44. Early… ASDs can often be detected as early as 18 months Children with an autism spectrum disorder might:  Not play "pretend" games (pretend to "feed" a doll)  Not point at objects to show interest (point at an airplane flying over)  Not look at objects when another person points at them  Have trouble relating to others or not have an interest in other people at all

45. Intervention… Research shows that early intervention can greatly improve a child’s development.  Behavioral and Educational Interventions  Complementary and Alternative Medicine  Dietary Changes  Medications 1] Handleman, J.S., Harris, S., eds. Preschool Education Programs for Children with Autism (2nd ed). Austin, TX: Pro-Ed. 2000. [2] National Research Council. Educating Children with Autism. Washington, DC: National Academy Press, 2001.

46. Sorting Through the “Breakthroughs” in Autism (adapted from D. Twachtman, Ph.D., CCC-SLP) Promise of a “cure”? Effective for everyone and any problem? Quality of the evidence for validity and effectiveness? Emotional and financial cost; benefit:cost ratio Harmful to the child? Emotional campaign and advertising? Are treatment gains truly meaningful?

47. Proposed “Cures” Separation from parents Holding therapy Yeast Free Diet Dietary restriction: Gluten/Casein Free Auditory Training Vision therapy (prism glasses) Chelation Vitamin Therapy (B6, C, B12) Secretin Magnetic Therapy Intravenous immunoglobulins Facilitated Communication Sensory Integration Probiotics Behavioral Intervention

48. Meantime, keep working towards the goals… Understand the genetics of autism…

49. Understand the environmental influences for autism… Keep working towards the goals…

50. Keep Counting… Keep Searching… Keep Treating And…

51. Thank You! For more information on CDC’s activities and other information related to autism: www.cdc.gov/autism The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

52. Acknowledgements Craig Newschaffer, Professor and Chairman of the Department of Epidemiology and Biostatistics at the Drexel University School of Public Health Aimee Anido, Project Coordinator Alana Aisthorpe, Abstractor Andrew Autry, Health Scientist Rachel N. Avchen, Epidemiologist Jon Baio, Behavioral Scientist Claudia M. Bryant, Abstractor Nancy Doernberg, Public Health Analyst Shryl Epps, Abstractor Susie Graham, Project Coordinator Nancy Hobson, Clinician Reviewer Marques Harvey, Project Coordinator Lekeisha Jones, Clinician Review Coordinator Rita Lance, Application Developer Charmaine MeKenzie, Research Assistant Catherine Rice, Behavioral Scientist Matthew Rudy, Abstractor Diana Schendel, Epidemiologist Darlene Sowemimo, Abstractor Melody Stevens, Community Liaison Ignae Thomas, Abstractor Kim Van Naarden -Braun, Epidemiologist Victoria Washington, Program Assistant Melissa Talley, Abstractor Lisa Wiggins, Health Scientist Susan Williams, Programmer Joanne Wojcik, Public Health Analyst Anita Washington, Project Coordinator Travis Williams, Abstractor