**Appendix**


**147**

*Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder…*

**Time of exposure**

(4-12y)

(15w)

(3-12y)

(15w)

(at birth)

(up to 6y)

Perinatal (at birth)

(4-12y)

(3-12y)

(10.1 ± 3.7y)

(7.5 ± 2.9y)

(11.0 ± 5y)

(7.5 ± 2.9y)

2ndtrimester

pregnancy)

trimester)

2ndtrimester

Long et al. 2019 75/135 Prenatal Amniotic fluid Decreased

2nd trimesters

Prenatal 1sttrimester

75/75 Prenatal 1 sttrimester

75/75 Prenatal (early

Perinatal (at birth)

35/30 Childhood

284/657 Perinatal

26/39 Childhood

45/50 Childhood

35/30 Childhood

Perinatal (at birth)

45/50 Childhood

**Exposure assessment**

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

quality

quality

Prenatal Geocoding/air

Prenatal Geocoding/air

**Risk**

Increased

Increased

Increased

Increased

Increased

Increased

Hair and nails Increased

Deciduous teeth Increased

Red blood cells Increased

Deciduous teeth Decreased

Hair Decreased

Hair and nailS Increased

Red blood cells Increased

Urine Increased

Serum Increased

Urine Increased

Serum Increased

Maternal serum Increased

Maternal serum Increased

Maternal serum Increased

Maternal serum Decreased

Maternal serum Increased

Maternal serum Increased

Geocoding/ pesticides data Decreased

Increased

**Ncontrols**

22101

348/ 78373

215/ 4856

Arora et al. 2017 22/54 Postnatal

22101

22101

Kardas et al. 2016 48/41 Childhood

Kardas et al. 2016 48/41 Childhood

Lyall et al. 2017 (2) 545/418 Prenatal (2nd

6975

Brown et al. 2018 778/778 Prenatal 1st or

Arora et al. 2017 22/54 Postnatal

*DOI: http://dx.doi.org/10.5772/intechopen.95758*

**Xenobiotic Study Ncases/**

von Ehrenstein et al. 2014

Talbott et al. 2015 (2)

El-Ansary et al.

Obrenovich et al.

Priya and Geetha

El-Ansary et al.

Roberts et al. 2013 325/

BPA Stein et al. 2015 46/52 Childhood

Phthalates Testa et al. 2012 48/45 Childhood

PBDEs Lyall et al. 2017 (1) 545/418 Prenatal

PFCs Lyall et al. 2018 553/443 Prenatal

2017

Mercury Windham et al. 2006

2011

2011

2017

PCBs Cheslack-Postava et al. 2013

OC pesticides Roberts et al. 2007 465/

Cheslack-Postava et al. 2013

Manganese Roberts et al. 2013 325/

Roberts et al. 2013 325/

Lead Priya and Geetha 2011


*Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder… DOI: http://dx.doi.org/10.5772/intechopen.95758*

*Autism Spectrum Disorder - Profile, Heterogeneity, Neurobiology and Intervention*

**Ncontrols**

55757

48731

428/ 6420

55757

Volk et al. 2013 279/245 Prenatal to

1522

1240

68139

428/ 6420

243949

979/ 14666

1240

68139

48731

68139

104/ 53181

215/ 4856

674/855 Prenatal 3 rdtrimester

Volk et al. 2014 251/156 Prenatal Geocoding/air

Talbott et al. 2015 217/226 Prenatal Geocoding/air

674/855 Postnatal

Volk et al. 2014 251/156 Prenatal Geocoding/air

**Time of exposure**

Prenatal to childhood

postnatal

Postnatal to childhood

Prenatal to Postnatal

Prenatal 1sttrimester

(1st year)

postnatal

Prenatal 3 rdtrimester

Postnatal to childhood

Prenatal to childhood

**Exposure assessment**

quality

quality

quality

quality

quality

quality

quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

quality

quality

quality

quality

quality

Postnatal (9 m) Geocoding/air

Postnatal (9 m) Geocoding/air

Prenatal Geocoding/air

Prenatal Geocoding/air

Geocoding/air quality

Geocoding/air quality

Geocoding/air quality

Prenatal Geocoding/air

Postnatal Geocoding/air

Prenatal Geocoding/air

Prenatal Geocoding/air

Postnatal (9 m) Geocoding/air

**Risk**

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

**Xenobiotic Study Ncases/**

O3 Becerra et al. 2013 5839/

Kaufman et al. 2019

McGuinn et al. 2020

PM2.5 Becerra et al. 2013 5839/

Jung et al. 2013 342/

Raz et al. 2015 245/

Chen et al. 2018 124/

Ritz et al. 2018 15387/

Jo et al. 2019 2471/

PM10 Volk et al. 2013 279/245 Prenatal to

Kaufman et al. 2019

McGuinn et al. 2020

Kalkbrenner et al.

Chen et al. 2018 124/

Ritz et al. 2018 15387/

Ritz et al. 2018 15387/

2015

SO2 Jung et al. 2013 342/

et al. 2014

Talbott et al. 2015 (2)

PAHs von Ehrenstein

**146**


**149**

**Table S1.**

*exposure).*

*Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder…*

**Time of exposure**

(5.3 ± 2.8y)

(7.4 ± 2.7y)

(8.2 ± 2.4y)

(10.6 ± 0.4y)

(3.7 ± 1.2y)

(5.5 ± 1.6y)

adulthood (18.9 ± 2.9y)

Prenatal to childhood

Childhood (5.4 ± 1.7y)

(7.0 ± 2.3y)

(4.9 ± 1.5y)

Arastoo et al. 2019 31/31 Childhood Serum Decreased

Neonatal Dried Blood

Neonatal Dried blood

83/106 Childhood Serum Decreased

100/100 Childhood Serum Decreased

54/36 Childhood Serum Decreased

Spots

spots

50/30 Childhood

18/19 Childhood

40/40 Early

Fernell et al. 2015 58/58 Neonatal Dried Blood

28/27 Childhood

**Exposure assessment** **Risk**

Serum Decreased

Serum Decreased

Serum Decreased

Serum Decreased

Serum Decreased

Serum Decreased

Serum Decreased

Medical records Decreased

Serum Decreased

Plasma Decreased

Serum Decreased

Decreased

Decreased

Decreased

Spots

**Ncontrols**

Tostes et al. 2012 24/24 Childhood

Gong et al. 2014 48/48 Childhood

Bener et al. 2014 254/254 Childhood

9882/ 499757

308

Guo et al. 2018 332/197 Childhood

1240

1607

*BPA – bisphenol A; d – days old; m – months old; NO2 – nitrogen dioxide; O3 – ozone; OC pesticides – organochlorine pesticides; OP pesticides – organophosphate pesticides; PAHs – polycyclic aromatic hydrocarbons; PBDEs – polybrominated diphenyl ethers; PCBs – polychlorinated biphenyls; PFCs – perfluorinated compounds; PM2.5 – particulate matter with a diameter less than 2.5* μ*m; PM10 – particulate matter with a diameter between* 

*Studies reporting xenobiotic exposure associated with ASD, identified through systematic literature review. For each study the numbers of ASD cases (Ncases) and controls (Ncontrols), the timing of exposure (specific time-points of prenatal, postnatal or childhood periods are shown when stated by the referenced authors), the exposure assessment method, and the direction of association are listed (increased or decreased risk by* 

*DOI: http://dx.doi.org/10.5772/intechopen.95758*

**Xenobiotic Study Ncases/**

Mostafa and AL-Ayadhi 2012

2013

Neumeyer et al.

Kocovska et al. 2014

Magnusson et al.

El-Ansary et al.

Alzghoul et al. 2019

Sengenc et al. 2020

Petruzzelli et al.

*2.5 and 10* μ*m; SO2 – sulfur dioxide; w – weeks old; y – years old.*

2020

Bener et al. 2017 308/

Wu et al. 2018 310/

Lee et al. 2019 1399/

2016

2018

Vitamin D Meguid et al. 2010 70/42 Childhood


*Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder… DOI: http://dx.doi.org/10.5772/intechopen.95758*

*BPA – bisphenol A; d – days old; m – months old; NO2 – nitrogen dioxide; O3 – ozone; OC pesticides – organochlorine pesticides; OP pesticides – organophosphate pesticides; PAHs – polycyclic aromatic hydrocarbons; PBDEs – polybrominated diphenyl ethers; PCBs – polychlorinated biphenyls; PFCs – perfluorinated compounds; PM2.5 – particulate matter with a diameter less than 2.5* μ*m; PM10 – particulate matter with a diameter between 2.5 and 10* μ*m; SO2 – sulfur dioxide; w – weeks old; y – years old.*

#### **Table S1.**

*Autism Spectrum Disorder - Profile, Heterogeneity, Neurobiology and Intervention*

**Ncontrols**

315

220

2961/ 35370

Pyrethroids Shelton et al. 2014 486/315 Prenatal Geocoding/

2961/ 35370

2961/ 35370

1507

43277

52150

421/ 464

249232

5437/ 630178

278

84906

44728

Al-Farsi et al. 2013 40/40 Childhood

Valproic Acid Moore et al. 2000 52 Prenatal Survey Increased

Bromley et al. 2013 12/509 Prenatal Interview and

100 Prenatal 1 sttrimester

> 1 sttrimester

Prenatal (early pregnancy)

Prenatal (early pregnancy)

(3-5y)

(2-3d)

Egorova et al. 2020 100/100 Prenatal Maternal serum Increased

86/1171 Postnatal

Nilsen et al. 2013 234/89602 Prenatal Medical records Decreased

Hicks et al. 2017 159/298 Prenatal Geocoding/

**Time of exposure**

Prenatal to postnatal

Prenatal to postnatal

Prenatal to postnatal

**Exposure assessment**

pesticides data

Prenatal Survey Increased

Geocoding/ pesticides data

pesticides data

pesticides data

Geocoding/ pesticides data

Geocoding/ pesticides data

Prenatal Medical records Increased

Prenatal Medical records Increased

Prenatal Medical records Increased

medical records

medical records

medical records

medical records

Medical records Increased

Interview Increased

Interview Decreased

Survey Decreased

Serum Decreased

Maternal plasma Increased

Prenatal Medical records Increased

Prenatal Medical records Decreased

Prenatal interview and

Prenatal Interview and

10/622 Prenatal Interview and

Prenatal Geocoding/

46/102 Prenatal Maternal urine Increased

**Risk**

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

Increased

**Xenobiotic Study Ncases/**

OP pesticides Shelton et al. 2014 486/

Philippat et al. 2018

von Ehrenstein et al. 2019

von Ehrenstein et al. 2019

Croen et al. 2011 298/

Rai et al. 2013 4429/

Gidaya et al. 2014 5215/

Rai et al. 2017 5378/

Harrington et al.

Bromley et al. 2008

Christensen et al.

Misoprostol Bandim et al. 2003 23 Prenatal

Surén et al. 2013 270/

Levine et al. 2018 572/

Raghavan et al. 2018

2015

2013

Folic Acid Schmidt et al. 2012 429/

Thalidomide Stromland et al. 1994

et al. 2019

Glyphosate von Ehrenstein

Antide pressants Schmidt et al. 2017 296/

**148**

*Studies reporting xenobiotic exposure associated with ASD, identified through systematic literature review. For each study the numbers of ASD cases (Ncases) and controls (Ncontrols), the timing of exposure (specific time-points of prenatal, postnatal or childhood periods are shown when stated by the referenced authors), the exposure assessment method, and the direction of association are listed (increased or decreased risk by exposure).*
