1. Changes in ASD Rates In Utah from 2002-2010: Explanations for increases? Judith Pinborough Zimmerman, Ph.D. Assistant Research Professor University of Utah judith.zimmerman@hsc.utah.edu

2. Background Autism spectrum disorders (ASDs) are a group of developmental disabilities characterized by impairments in social interaction and communication, as well as restricted, repetitive, and stereotyped patterns of behavior Cause is unknown ▫Genetics and environmental susceptibility Challenges in determining the prevalence of autism More affected versus more detected?

3. ASD Prevalence: Who, where, and how you count counts Retrospective record reviews (Centers for Disease Control and Prevention Autism and Developmental Disabilities Monitoring Network) ▫1 in 47 in 2008 study year Administrative counts Surveys Direct Screening and Assessment

4. ADDM ASD Prevalence per 1000 Children

5. Identified ASD Prevalence per 1,000 Variation across Sites in Identified Prevalence of ASDs ADDM Network, 14 Sites, 2008 (MMWR, 2012) Health-Only Records Access Education & Health Records Access

6. Change in Identified Utah ASD Prevalence by Sex

7. Change in Identified Utah ASD Prevalence by Intellectual Ability

8. Associated Features Eating Sleeping Mood Discrepancy in cognitive profile Aggression Oppositional Motor delays Hyperactivity Lack or excessive fear Odd responses to sensory stimuli Self injurious behavior Seizures/staring spells Temper tantrums

9. Earliest Known Utah ASD Diagnosis Median Age and Proportion by Diagnostic Subtype Subtype of Earliest Diagnosis: Autistic Disorder ASD/PDD Asperger Disorder Distribution of Subtypes: 42%45%13% Median Age of Earliest Diagnosis: 52 Months 68 Months Limitations: 1)Diagnostic information obtained from evaluation records may not capture the exact age of each child’s earliest diagnosis 2)Instability of diagnostic subtypes over time

10. Utah ASD Administrative Prevalence 2002* 2006* 2008* 2010 † Age 8 4 6 8 4 6 8 4 6 8 Population Size 26,213 33,955 32,801 29,494 35,803 34,368 33,210 37,066 37,134 36,201 Cases 171 256 322 301 293 418 432 342 508 573 Prevalence (per 1,000) 6.5 (1 in 153) 7.5 (1 in 133) 9.8 (1 in 102) 10.2 (1 in 98) 8.2 (1 in 122) 12.2 (1 in 82) 13.0 (1 in 77) 9.2 (1 in 108) 13.7 (1 in 73) 15.8 (1 in 63) * 2002-2008 includes Davis, Salt Lake, and Utah counties. † 2010 includes Davis, Salt Lake, Tooele, and Utah counties. Source: Pinborough-Zimmerman, J., Intveld, A., Kingsbury, C.M.B. Changes in the Administrative Prevalence of Autism Spectrum Disorders in Utah from 2002-2010, University of Utah, 2012.

11. Utah ASD Administrative by Gender

12. ASD Prevalence: Use of surveys Survey: caregiver report of ASD diagnosis. ▫2011 National Survey of Children’s Health telephone survey found 2% of 6 to 17 year olds had a diagnosis of ASD compared to the 2007 estimate of 1.16 % ▫Increase was greater for boys than girls, and among 14-17 years olds than younger children ▫Attribute change to doctors better identifying the disorder

13. ASD Prevalence: Direct Assessment Direct Assessment: Screening & comprehensive assessment of a population by clinicians. The “gold standard”. Kim et al., (Am J Psychiatry, 2011) screened and evaluated 7-12 year olds in a town in South Korea (n=55,000). Reported a prevalence of 1 in 38 or 2.64% Brugha et al., (Arch Gen Psychiatry, 2011 ) conducted diagnostic assessments in an adult population in England (n=7461) and found 1% prevalence without a significant reduction in the older part of the sample

14. Factors that may influence ASD prevalence trends Intrinsic Identification: internal methodology or measurement factors Extrinsic Identification: external classification and awareness factors involved in identifying people with ASD in a population Risk: Possible etiologic or true change in ASD symptoms among the population

15. Factors Explaining increase in ASD prevalence

16. Chemical Pollutants and Autism Traffic related air pollution ▫Volk et al (JAMA, 2013) Exposure to traffic related air pollution, nitrogen dioxide, PM2.5 and PM 10 during pregnancy was associated with autism (AOR, 1.98 during gestation and 3.10 during first year of life) ▫Becerra et al., (Environ Health Perspect, 2013) Association between autism and prenatal air pollution exposure related to traffic sources ▫Windham et al ((Environ Health Perspect, 2013) potential association between autism and estimated metal concentrations and possibly solvents in ambient air around birth residence

17. Maternal Residential Proximity to Toxic Release Inventory Sites Identified by 2002 UT-ADDM (CDC, 2007; Pinborough- Zimmerman, et al, 2009; Pinborough-Zimmerman, et al., 2007) Children living in Salt Lake, Davis, or Utah Counties in 2002 (born in 1994) Cases were matched to Utah birth records using a deterministic and probabilistic hybrid approach 99% of maternal birth addresses geocoded for cases and controls

18. Toxic Release Inventory Sites Sites listed in a publicly available EPA database ▫contains information on toxic chemical releases and waste management activities reported annually ▫TRI sites operational in 1993- 1994 with annual reportable emissions of heavy metals (arsenic, cadmium, lead, nickel, and mercury) and halogenated chemicals (dioxins, PCB’s, trichloroethylene) ▫Geocoded sites (n=54) (EPHT)

19. Chemicals ChemicalSuspected Neurologica l Toxicant Recognized Development al Toxicant Suspected Endocrine Toxicant Heavy Metals ArsenicYes CadmiumYes LeadYes NickelYesND MercuryYes Halogenated Chemicals DioxinND Yes PCBsND Yes Trichloroethylene YesND

20. Chemical Type and Poundage Type of Exposure Contaminant Level 1 = Heavy Metals 1 = < 250 lbs 2 = Halogenated Chemicals 2 = > 250 < 5,000 lbs 3 = Both3 = > 5,000 < 10,000 lbs 4 = > 10,000 lbs

21. TRI sites by type of contaminant and poundage level TRI site typeTRI site (N)ASD (N)ID (N)CD (N)ADHD (N)Birth Cohort (N) Heavy metal < 250 lbs7yes 1843 > 250 lbs < 5,000 lbs6yes 571 > 5000 lbs < 10,000 lbs000000 > 10,000 lbs000000 Halogenated chemicals < 250 lbs2yes 269 > 250 lbs < 5,000 lbs100000 > 5000 lbs < 10,000 lbs5yes 338 > 10,000 lbs28yes 3618 Halogenated chemicals and heavy metals < 250 lbs000000 > 250 lbs < 5,000 lbs000000 > 5000 lbs < 10,000 lbs000000 > 10,000 lbs5yes 0411 Total54yes 7050

22. Analysis Primary Aim: ▫Created buffer zones (¼, ½ and 1 mile) around TRI facilities ▫Compared the proportion of cases vs. controls by buffer distance, case type, chemical group, and poundage level ▫Tested for significant difference

23. Annual Reportable Emissions No. of TRI sites (n=54) No. of Controls living within 1 mile radius of TRI site (n=7050)Speech-Language Impaired (838) Heavy metalsP-valueOdds Ratios Confidence Interval < 250 lbs718430.170.80.58-1.10 > 250 lbs < 5000 lbs65710.350.780.47-1.31 > 5000 lbs < 10,000 lbs00*** > 10,000 lbs00*** Halogenated chemicals < 250 lbs22690.230.580.24-1.42 > 250 lbs < 5000 lbs10*** > 5000 lbs < 10,000 lbs53380.531.210.67-2.16 > 10,000 lbs2836180.050.80.64-1 Halogenated chemicals and heavy metals < 250 lbs00*** > 250 lbs < 5000 lbs00*** > 5000 lbs < 10,000 lbs00*** > 10,000 lbs54110.41.220.74-2.02

24. Annual Reportable Emissions No. of TRI sites (n=54) No. of Controls living within 1 mile radius of TRI site (n=7050)Intellectual Disability (n=113) Heavy metalsP-valueOdds Ratios Confidence Interval < 250 lbs718430.510.740.30-1.81 > 250 lbs < 5000 lbs65710.022.831.31-6.11 > 5000 lbs < 10,000 lbs00*** > 10,000 lbs00*** Halogenated chemicals < 250 lbs22690.321.750.43-7.14 > 250 lbs < 5000 lbs10*** > 5000 lbs < 10,000 lbs53380.053.051.12-8.32 > 10,000 lbs2836180.021.741.10-2.75 Halogenated chemicals and heavy metals < 250 lbs00*** > 250 lbs < 5000 lbs00*** > 5000 lbs < 10,000 lbs00*** > 10,000 lbs54110.71.130.28-4.59

25. Annual Reportable Emissions No. of TRI sites (n=54) No. of Controls living within 1 mile radius of TRI site (n=7050)Autism Spectrum Disorders (99) Heavy metalsP-valueOdds Ratios Confidence Interval < 250 lbs718430.130.330.08-1.34 > 250 lbs < 5000 lbs65710.082.280.92-5.63 > 5000 lbs < 10,000 lbs00*** > 10,000 lbs00*** Halogenated chemicals < 250 lbs22690.2720.49-8.19 > 250 lbs < 5000 lbs10*** > 5000 lbs < 10,000 lbs53380.033.51.28-9.57 > 10,000 lbs2836180.00072.181.37-3.45 Halogenated chemicals and heavy metals < 250 lbs00*** > 250 lbs < 5000 lbs00*** > 5000 lbs < 10,000 lbs00*** > 10,000 lbs54110.671.290.32-5.26

26. Annual Reportable Emissions No. of TRI sites (n=54) No. of Controls living within 1 mile radius of TRI site (n=7050)All Groups Combined Heavy metalsP-valueOdds Ratios Confidence Interval < 250 lbs718430.070.760.57-1.02 > 250 lbs < 5000 lbs65710.241.250.86-1.8 > 5000 lbs < 10,000 lbs00*** > 10,000 lbs00*** Halogenated chemicals < 250 lbs22690.81.080.6-1.93 > 250 lbs < 5000 lbs10*** > 5000 lbs < 10,000 lbs53380.031.621.04-2.5 > 10,000 lbs2836180.9610.83-1.2 Halogenated chemicals and heavy metals < 250 lbs00*** > 250 lbs < 5000 lbs00*** > 5000 lbs < 10,000 lbs00*** > 10,000 lbs54110.511.160.74-1.83

27. Strengths Completeness of case ascertainment Population-based sample Geocoded maternal addresses for cases and controls Site specific addresses of TRI sites, chemical and poundage type Multiple measures of SES

28. Limitations Addresses for the first trimester of pregnancy are unknown Exposure estimates do not include other sources of chemical exposures Chemical concentrations represent annual measures by site No actual personal measurements in subjects Unable to take into account mobility or specific maternal activities Findings are preliminary and further analysis needed

29. Service and Research Implications Better identification among certain subgroups ▫Still concerned about disparities in identified prevalence  Across sites (methodological: access to records / geographic: access to care)  Among children of minority race/ethnicity, low socioeconomic status More children than ever are being recognized as having ASDs Still concerned that 20% are not classified with autism by community providers, others are not recognized as early as they can be Need to accelerate our research into risk factors and causes of ASD ▫Highlights the need for further scientific investigation into the potential association of exposure to hazardous air pollutants and increased risk of ASD and other developmental disabilities