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. 2016 Sep 21;11(9):e0161851. doi: 10.1371/journal.pone.0161851

Table 2. Characteristics of included human studies on air pollution and ASD, by publication date and study design.

Study Study design Study population & location Sample size Exposure assessment Outcome assessment
Windham et al. 2006 [55] Case-control Children born in 1994 in 6 counties in the San Francisco Bay area 284 children with ASD and 657 controls Modeled concentrations of 29 hazardous air pollutants in 1996,a assigned by census tract of maternal residence at delivery (birth cert) ASD cases ascertained from multi-source records-based surveillance of children, conducted by California CADDRE (within CDPH)
Roberts et al. 2007 [48] Case-control Children born between 1996–1998 in 19 counties in the Central Valley of California 465 children with ASD and 6,975 controls Modeled concentrations of 54 pesticides applied between 1995–1998,b assigned by maternal residence of maternal residence at delivery (birth cert) ASD cases identified (by CDPH) from CA Dept of Developmental Services (DDS) files
Windham et al. 2007 [56] Case-control Children born between 1996–1998 in 4 counties in Southern California 3,400 children with ASD and controls frequency matched on last menstrual period in a 1:10 ratio Modeled concentrations of 29 hazardous air pollutants in 1996,a assigned by census tract of maternal residence at delivery (birth cert) ASD cases identified (by CDPH) from CA Dept of Developmental Services (DDS) client files
Lewandowski et al. 2009 [45] Ecological Students in Texas school districts for academic years 2000–2001 through 2005–2006 7,022 children with ASD and 4,050,690 controls for 2001; numbers not reported for other years Modeled concentrations of 11 toxic release pollutants in 2001 and of mercury only between 2000–2005,c assigned by school district Prevalence of ASD and other special education categories obtained from the Texas Education Agency Academic Excellence Indicator System
Kalkbrenner et al. 2010 [43] Case-control Children aged 8 years in North Carolina (born in 1994 and 1996) and West Virginia (born in 1992 and 1994) 383 children with ASD and 2,829 children with speech and language impairment as controls Modeled concentrations of 35 hazardous air pollutants in 1996,a assigned by census tract of birth residence ASD cases and controls with speech and language impairment identified from records-based surveillance of children conducted by ADDM
Trousdale et al. 2010 [50] Case-control All children aged 8 years in the US (specifically in MD for sub-analysis) during school years 2004–2005 and 2007–2008 Not reported Modeled concentrations of 34 hazardous air pollutants in 1996 and 89 hazardous air pollutants in 1999,a assigned over entire U.S (and for MD state by county in sub-analysis) ASD prevalence calculated using data from the U.S. Department of Education, Office of Special Education Programs and control numbers using data from the National Center for Education Statistics enrollment data (Maryland sub-analysis from Maryland State Department of Education)
Blanchard et al. 2011 [40] Ecological Students in Bexar County, TX (all ages) and Santa Clara County, CA (elementary school ages) in 2008 Not reported Modeled concentrations of mercury in 2002,a assigned by city block-level school districts ASD rates obtained from the Texas Education Association and from http://www.kidsdata.org for California
Volk et al. 2011 [51] Case-control Children enrolled in the CHARGE study and born between 1997–2006 in California 304 children with ASD and 259 typically developing controls Distance to freeways and major roads as proxy for traffic-related pollutant exposure; assigned by residential address during pregnancy and at birth ASD cases identified from California DDS and children evaluated and diagnosed by study staff using the ADI-R and ADOS tools; controls were selected based on SCQ
McCanlies et al. 2012 [46] Case-control Children enrolled in the CHARGE study and born between 1998–2003 in California 93 children with ASD and 81 typically developing controls Self-reported and industrial hygienist-assessed parental occupational exposures to 49 chemical agents from three months prior to conception through to either birth or weaning for breast-fed children ASD cases recruited by California DDS and children evaluated and diagnosed using the ADI-R and ADOS tools; controls were selected based on SCQ
Becerra et al. 2013 [39] Case-control Children born in 1994–2006 in Los Angeles County, CA 7,603 children with ASD and 75,782 controls Modeled concentrations of 6 pollutants between 1993–2006,d assigned by residential address at delivery/birth Autistic disorder cases identified from records of California DDS
Pino-Lopez and Romero-Asuyo 2013 [47] Case-control Children aged 12–36 months evaluated by the Early Intervention Service in Ciudad Real, Spain between January 2009 and February 2011 70 children with ASD and 136 unaffected controls Self-reported parental occupation to evaluate exposure to solvents during pregnancy ASD cases and unaffected controls identified through the Early Intervention Service of Ciudad Real
Volk et al. 2013 [52] Case-control Children enrolled in the CHARGE study and born between 1997–2006 in California 279 children with ASD and 245 typically developing controls Modeled concentrations to traffic-related air pollution between 1997–2008 and monitoring data for 4 pollutants using regional air quality data between 1997–2009,d,e assigned by self-reported residence history address during pregnancy and the first year of the child’s life ASD cases identified from California DDS files, children evaluated and diagnosed by study staff using the ADI-R and ADOS tools; controls were selected based on SCQ
Windham et al. 2013 [57] Case-control Children born in 1994 in 6 counties in the San Francisco Bay area 284 children with ASD and 659 controls Self-reported parental occupation on birth certificate, coded by occupational medicine-certified physician to categorize broad chemical exposures ASD cases ascertained from multi-source records-based surveillance of children conducted by California CADDRE
Jung et al. 2013 [42] Cohort Children aged less than 3 years in 2000 enrolled in prospective cohort study in Taiwan 342 children with ASD and 48,731 non-ASD controls Modeled concentrations of pollutants between 1996–2009,d assigned by post-code levels in the 1–4 years preceding ASD diagnosis ASD and non-ASD children in cohort identified based on diagnosis codes provided in the Taiwan National Insurance Research Database
Roberts et al. 2013 [49] Cohort Children of Nurses’ Health Study II participants born between 1987–2002 in the US 325 children with ASD and 22,098 controls Modeled concentrations of 14 ambient hazardous air pollutants between 1990–2002,a assigned by census tract by mother’s address approximately around the year of birth ASD cases identified based on Nurses’ Health Study II participant’s response to questionnaire, validated by administration of the ADI-R to a small, random subset of case mothers
Gong et al. 2014 [41] Case-control Twins born after July 1, 1992 and enrolled in the CATSS longitudinal study in Stockholm, Sweden 109 children with ASD and 3,051 healthy controls Modeled historical emissions to estimate exposures for two pollutants (PM10 and NOx) between 1992–2009, assigned by residential address during pregnancy, child’s first year of life, and the year before ASD diagnosis ASD cases and controls identified after assessment using A-TAC tool at 9 and 12 years of age conducted by the CATSS
Shelton et al. 2014 [58] Case-control Children enrolled in the CHARGE study and born after 2003 in California 486 children with ASD and 315 typically developing children as controls Modeled concentrations of 4 classes of pesticides between 1997–2008,b assigned by prenatal and birth residential address ASD cases identified from California DDS files, children evaluated and diagnosed using the ADI-R and ADOS tools by study staff; controls were selected based on SCQ
Volk et al. 2014 [53] Case-control Children enrolled in the CHARGE study in California 251 children with ASD and 156 controls Modeled concentrations to traffic-related air pollution and monitoring data for 4 pollutants using regional air quality data between 1997–2009,e,f assigned by prenatal and birth residential address ASD cases identified from California DDS files, children evaluated and diagnosed by study staff using the ADI-R and ADOS tools; controls were selected based on SCQ
von Ehrenstein et al. 2014 [54] Case-control Children born between 1995–2006 in Los Angeles County 768 children with ASD and 147,954 controls Monitoring data for 24 hazardous air pollutants within a 5-km radius of birth address Cases identified from California DDS files of children served for autistic disorder
Raz et al. 2014 [61] Case-control Children of Nurses’ Health Study II participants born between 1990–2002 in the US 245 children with ASD and 1,522 controls Modeled concentration from monitoring data for two pollutants (PM10 and PM10-2.5),f Assigned by prenatal, pregnancy and birth residential address ASD cases identified based on Nurses’ Health Study II participant’s response to questionnaire, and validated by administration of the ADI-R to a random subset of case mothers
Kalkbrenner et al. 2015 [44] Case-control Children born in North Carolina in 1994 (8 counties), 1996 (8 counties), 1998 (9 counties), and 2000 (10 counties) and born in 6 San Francisco Bay area counties in 1996 645 children with ASD and 12,434 controls for North Carolina and 334 children with ASD and 2,232 controls for California Modeled concentration of one pollutant from monitoring data,f assigned by birth certificate address ASD cases identified from multi-source records-based surveillance of children conducted by the ADDM in North Carolina and California CADDRE
Dickerson et al. 2015 [59] Ecological Children 8 years of age in 2000, 2002, 2004, 2006 and 2008 from Arizona, Maryland, New Jersey, South Carolina, and Utah 4,486 children with ASD from 2489 census tracts Modeled concentrations of 3 toxic release pollutants between 1991–1999,c assigned by census tract using residence at the time of surveillance (8 years of age) ASD cases identified from records-based surveillance of children conducted by ADDM network
Dickerson et al. 2016 [60] Ecological Children 8 years of age in 2000, 2002, 2004, 2006 and 2008 from Arizona, Maryland, New Jersey, South Carolina, and Utah 4,486 children with ASD from 2489 census tracts Modeled concentrations of 3 hazardous air pollutants in 1999,a assigned by census tract at the time of surveillance (8 years of age) ASD cases identified from records-based surveillance of children conducted by ADDM network

a Data from US EPA National-scale Air Toxics Assessment (NATA);

b Data from California Department of Pesticide Regulation (DPR);

c Data from US Toxic Release Inventory (TRI);

d Data from nearest air monitoring stations;

e Data from CALINE4 dispersion model;

f Data from US EPA Air Quality System (AQS)

Abbreviations: ADDM, Autism and Developmental Disabilities Monitoring; ADI-R, Autism Diagnostic Interview, Revised; ADOS, Autism Diagnostic Observation Schedule; AQS, Air Quality System; ASD, autism spectrum disorder; A-TAC, Autism Tics, ADHD, and other Comorbidities inventory; CADDRE, Centers for Autism and Developmental Disabilities Research and Epidemiology; CALINE4, California Line Source Dispersion Model, version 4; CATSS, Children from the Child and Adolescent Twin Study in Sweden; CHARGE, Childhood Autism Risks from Genetics and the Environment; CDPH, CA Department of Public Health; DDS, Department of Developmental Services; NIOSH, National Institute for Occupational Safety and Health; SCQ, Social Communication Questionnaire; TRI, Toxics Release Inventory; USC, University of Southern California