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Data Sources For the US, autistic disorder data were obtained from the California Department of Developmental Services (DDS) [1] [2] [3] and from the Individuals with Disabilities Education Act (IDEA) program website of the Department of Education [4].1234 Live birth data were extracted from the CDC’s “Annual reports of Vital Statistics of the United States”, [5] [6] and birth year AD prevalence per 10,000 was then calculated.5] [6 Male population data were obtained from the U.S. Census Bureau website, [7] for data prior to 2000 and from the “factfinder” web site for data after 2000 [8]. Birth rates by age of father were obtained from the National Vital Statistics Reports: “Birth Final Data” [9].789 MMR, Varicella and Hepatitis A immunization coverage for children 19 to 35 months of age was obtained from the CDC National Immunization Survey (NIS) [10].10 Methods

Changepoint Analysis Linear regression and R 2 analyses were used to assess correlations between AD prevalence and vaccine coverage or births by paternal age; associations with P<0.05 were considered significant. For CP determination, both the hockey-stick [1] and segmented line fitting [2] methods were employed. The robustness of our algorithm was tested by repeating the algorithm using deliberately chosen poor initial inputs.12 Methods

Diagnostic and Statistical Manual Diagnostic and Statistical Manual (DSM) editions were checked for printing dates, found on the copyright page. This information was used as an indication of the rapidity with which changes in diagnostic criteria were embraced by the professional community. To determine whether DSM revisions might be related to changes in AD diagnosis rates, we predicted a range of AD changepoint birth years based on the printing dates for the various DSM revisions. Our assumptions were that the earliest age of autism diagnosis is 3 years and that by 8 years of age diagnosis is stable; therefore, a DSM revision would be predicted to induce a changepoint between 8 years prior to the earliest print date and 3 years prior to the latest print date. [1] [2].1] [2]. Methods

Thimerosal Containing Vaccines A historical analysis of TCVs was conducted to determine the years in which changes to the thimerosal load received by vaccinated children occurred. Assuming that increased thimerosal load is related to AD we predicted AD changepoints based on FDA approval of new vaccines or new dosing schedules of TCVs and compared these predicted changepoint ranges to the actual calculated changepoints for AD. Methods

AD Rate AD Changepoints Vaccines Paternal Age Thimerosal Diagnostic Substitution Polio MMRVaricella Hep A 3 yr olds 8 yr olds Individual BYr Combined Data Criteria Schedules Newschaffer All vaccines THE UNITED STATES (Click on the graphs under each topic)

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Calculated AD Changepoints US , 19 yr olds US 1992 – 2003, 8 yr olds CA , 5 yr olds & CA , 4 yr olds Go Back to Main Page

AD Changepoints US , 19 yr olds US 1992 – 2003, 8 yr olds CA , 5 yr olds CA , 4 yr olds Go Back to Main Page

TABLE OF POLIO VACCINES POLIO VACCINES AND AD CHANGEPOINTS POLIO VACCINES Go Back to Main Page (Click on the graphs under each topic) Go Back to Main Page

POLIO VACCINES IN US CellsNotesCompany FDA Approval End yearTrade Name Age of immunization Comments MRC-5 OPVPfizer DIPLOVAX6-12 weeks never caught on among U.S. pediatricians IPVSanofi-Pasteur11/20/ POLIOVAX 2,4,6, months IPV 2008NowPENTACEL 2,4,6, months Vero cell line * IPVSanofi-Pasteur12/21/1990NowIPOL 2, 4, months, and 4-6 years IPVGSK12/13/2002NowPEDIARIX2, 4, 6 months Source * The Vero lineage was isolated from kidney epithelia cells extracted from an African green monkey Polio main page Go Back to Main Page

POLIO VACCINES CellsNotesCompany FDA Approval End yearTrade NameAgeComments MRC-5 OPVPfizer DIPLOVAX6-12 weeks never caught on among U.S. pediatricians IPVSanofi-Pasteur11/20/ POLIOVAX2,4,6, months IPV 2008NowPENTACEL2,4,6, months POLIOVAX Polio main page Go Back to Main Page

A.“SIMIAN VIRUS 40 (SV40): A POSSIBLE HUMAN POLYOMAVIRUS WORKSHOP - MONDAY, 27 JANUARY, 1997” B.Immunogenicity Review of Pentacel from FDA BLA STN # (POLIOVAX), approved November 20, 1987 C.CDC list of Discontinued Vaccine in US ( ) Poliovax was used from D.Procedure of manual school immunization - Department of Health ( ) Trivalent Oral Polio Vaccine - June 25, 1963 e-IPV - December 22, 1987 IPV - Used from Poliovax -polio virus vaccine, enhanced, inactivated vaccine (e-IPV), Pasteur-Merieux- Connaught ( discontinued 1991 ) Back Polio main page Go Back to Main Page

Measles, Mumps and Rubella MMR vaccine information table MMR and AD changepoints (Click on the graphs under each topic) Go Back to Main Page

MEASLES, MUMPS, RUBELLA, VARICELLA 01/1979Meruvax IIA rubella vaccine with the RA 27/3 Merck>=12 monthsLicensed. 1979MMR IICombined measles, mumps and rubella with the RA 27/3 strain Merck>=12 months Licensed 1989MMR IICombined measles, mumps and rubella with the RA 27/3 strain Merck>=12 months2 nd dose Go Back to Main Page MMR main page

MEASLES, MUMPS, RUBELLA, VARICELLA 01/1979Meruvax IIA rubella vaccine with the RA 27/3 Merck>=12 monthsLicensed. 1979MMR IICombined measles, mumps and rubella with the RA 27/3 strain Merck>=12 months Licensed 1989MMR IICombined measles, mumps and rubella with the RA 27/3 strain Merck>=12 months2 nd dose Meruvax II MMR II MMR II 2 nd dose Go Back to Main Page MMR main page

Varicella Uptake of Varicella for All States for 35 monhs old born between 1992 through 2007 U.S. AD vs Varicella for 8 years old born between All States AD vs Varicella for 8 years old born between Normalized Varivax immunizations vs Normalized Autism Disorder cases for 8 year olds for birth year Varicella vaccine and AD Changepoint Go Back to Main Page (Click on the graphs under each topic)

Varicella main page Hep A recommended/ considered in 17 states Go Back to Main Page

Varicella main pageGo Back to Main Page

Varicella main page Go Back to Main Page

Varicella main page Go Back to Main Page

VARICELLA 3/17/1995VarivaxVaricella virus vaccine, liveMerck>=12 monthsLicensed Varivax Varicella main page Go Back to Main Page

Hepatitis A Table of Hepatitis A vaccines approved in the US. Hepatitis A immunization coverage for 35 months old born between Hepatitis A immunization case vs AD cases for children born Go Back to Main Page (Click on the graphs under each topic)

History of Hepatitis A vaccines approved for use in the U.S. 2/22/1995HavrixThe first inactivated hepatitis A vaccine SmithKline Beecham >=24 monthsLicensed 3/29/ Vaqta A second inactivated hepatitis A vaccine 17 states rec/considered for use Merck>=24 months Licensed 5/11/2001Twinrix A combined hepatitis A inactivated and hepatitis B (recombinant) vaccine SmithKline Beecham >=18 yearsLicensed 8/11/ Vaqta A second inactivated hepatitis A vaccine Included in ACIP recommendations Merck>=12 months FDA approved lowering the age limit to 12 months 10/18/2005Havrix The inactivated hepatitis A vaccineGSK>=12 months FDA approved lowering the age limit to 12 months 3/28/2007TwinrixA combined hepatitis A inactivated and hepatitis B (recombinant) vaccine GSK>=18yearsFDA approved an accelerated dosing schedule. Hep A main page Go Back to Main Page

Hep A main page Go Back to Main Page

Hep A main page Go Back to Main Page

Paternal Age Absolute Live births and AD cases grouped by age of father from Absolute live births from grouped by paternal age AD prevalence & live births to fathers aged 40 – 44 from 1960 to 2002 (Click on the graphs under each topic) Go Back to Main Page

Paternal age Main topics

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, , , , , , AD prevalence & live births to fathers aged 40 – 44 from 1960 to 2002 # Live Births to yr oldsUS Autism DisorderPredicted 1960 AD rate Go Back to Main Page Paternal age Main topics

Thimerosal containing vaccines and national vaccination schedule from 0-18 months Go Back to Main Page

Table 1- Comparison of diagnostic criteria for autistic disorder (AD) across DSM revisions Go Back to Main Page

Table 2 - Printing schedules for DSM revisions/editions Date of printingNumber printedPredicted BYr CP range by DSM printingsCalculated BYr CP DSM III Feb-8040,000 Feb 1972-Sep * May-8025,000 Sep-8025,000 Nov-8030,000 Jan-8130,000 Mar-8135,000 Sep-8125,000 DSM IIIR May-8775,000 May 1979 –Nov Jun-8780,000 Nov-8775,000 DSM IV May-94 Jul-94 Aug-94 Jan-95 not given May Jan Go Back to Main Page

National Autism Prevalence Trends From United States Special Education Data Craig J. Newschaffer, Matthew D. Falb and James G. Gurney Go Back to Main Page

1. Qian S (2010) Environmental and Ecological Statistics with R. Boca Raton, FL: Chapman & Hall/CRC. 2. Muggeo VM (2008) segmented: an R Package to Fit Regression Models with Broken-Line Relationships. R News. pp Back

1. McDonald ME PJ (2010) Timing of increased autistic disorder cumulative incidence. Environ Sci Technol 44: Cavagnaro AT. Autistic Spectrum Disorders. Changes in California Caseload. An Update: 1999 through California Health and Human Services Agency Schechter R, Grether JK. Continuing increases in autism reported to California's developmental services system: mercury in retrograde. Arch Gen Psychiatry 2008;65: Individuals with Disabilities Education Act (IDEA) (2012). Child Count Data. Available: Accessed September Centers of Disease Control and Prevention. Vital Statistics of the United States. Available: Accessed September Centers of Disease Control and Prevention (2012). Vital Statistics Data - Births. Available: Accessed September US Census Bureau (2012). Population Estimates. Available: Accessed September US Census Bureau. American Fact Finder. Available: Accessed September Centers of Disease Control and Prevention (2012). National vital Statistics System. Available: Accessed September Centers of Disease Control and Prevention (2012).U.S. Vaccination Coverage Reported via NIS. Available: Accessed September Back

1. Lord C, Risi S, DiLavore PS, Shulman C, Thurm A, Pickles A. (2006) Autism From 2 to 9 Years of Age. Arch Gen Psychiatry 63: Luyster R, Gotham K, Guthrie W, Coffing M, Petrak R, Pierce K, Bishop S, Esler A, Hus V, Oti R, Richler J, Risi S, Lord C. (2009) The Autism Diagnostic Observation Schedule-toddler module: a new module of a standardized diagnostic measure for autism spectrum disorders. J Autism Dev Disord 39: Back