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Craig Newschaffer Director, AJ Drexel Autism Institute Drexel University Four things you should know about environmental autism risk factors

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Page 1: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Craig NewschafferDirector, AJ Drexel Autism Institute

Drexel University

Four things you should know about environmental autism risk factors

Page 2: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Outline

What is a “risk factor”

What is “environment”① Environmental risk factors do contribute to causing

autism

② Environmental risk factors are challenging for scientists to discover and confirm

③ The amount of increased risk any one environmental risk factor conveys to the individual is likely quite small

④ However, the overall impact in the population can be quite large

Environmental risk factors with supporting evidence under study now

Time for questions

Page 3: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

What is a “risk factor”?

Something that affects the chance of an outcome

chance = probability

…so, there is some math thinking involved.

Page 4: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

What does a 30% chance of rain mean?

Page 5: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

What is a “the environment”?

Everything that is not heritable…

Page 6: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute
Page 7: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

① Environmental risk factors do contribute to causing autism

Page 8: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

① Environmental risk factors do contribute to causing autism

Family studies contrast recurrence of a condition among family members of different known “relatedness” to estimate heritability

Autism twin studies

Heritability estimates from modern twin studiestend to be 50%-60%, with some (higher) exceptions

Other recent family studies generated higher (>80%) heritability estimates

Page 9: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

GENES

ENVIRONMENT

Page 10: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Multifactorial causation

Z YS

TU V

X

W

① Environmental risk factors do contribute to causing autism

Page 11: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Single factor causation

G

① Environmental risk factors do contribute to causing autism

Page 12: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Gene-environment interaction

G E

① Environmental risk factors do contribute to causing autism

Page 13: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Gene-environment interaction

G E

Heritability in family studies is over-estimated

① Environmental risk factors do contribute to causing autism

Page 14: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Dev Med Child Neurol, 1994

Stromland et al. Dev Med Child Neurol 1994

Proof of principle exposure example

① Environmental risk factors do contribute to causing autism

Page 15: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

② Environmental risk factors are challenging for scientists to discover and confirm

Page 16: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

The environment is everything that is not heritable…

② Environmental risk factors are challenging for scientists to discover and confirm

Page 17: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

8-10 synthesized chemicals proven as developmental

neurotoxicants

Source: Landrigan and Goldman Health Aff 2012

② Environmental risk factors are challenging for scientists to discover and confirm

Page 18: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

200 detected in blood/urine of all

Americans

8-10 synthesized chemicals proven as developmental

neurotoxicants

Source: Landrigan and Goldman Health Aff 2012

② Environmental risk factors are challenging for scientists to discover and confirm

Page 19: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

200 detected in blood/urine of all

Americans

8-10 synthesized chemicals proven as developmental

neurotoxicants

Source: Landrigan and Goldman Health Aff 2012

② Environmental risk factors are challenging for scientists to discover and confirm

However<20% detectable chemicals adequately screened for neurodevelopmental effects

Page 20: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

3,000 high volumechemicals

200 detected in blood/urine of all

Americans

8-10 synthesized chemicals proven as developmental

neurotoxicants

Source: Landrigan and Goldman Health Aff 2012

② Environmental risk factors are challenging for scientists to discover and confirm

However<20% detectable chemicals adequately screened for neurodevelopmental effects

Page 21: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

80,000 new synthesized chemicals

3,000 high volumechemicals

200 detected in blood/urine of all

Americans

8-10 synthesized chemicals proven as developmental

neurotoxicants

Source: Landrigan and Goldman Health Aff 2012

② Environmental risk factors are challenging for scientists to discover and confirm

However<20% detectable chemicals adequately screened for neurodevelopmental effects

Page 22: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Source: Yuen et al. Nat Neurosci 2018

② Environmental risk factors are challenging for scientists to discover and confirm

Interrogation of the whole genome (genomics) is now common

Page 23: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

② Environmental risk factors are challenging for scientists to discover and confirm

Interrogation of the whole “exposome” in its earliest days

Rappaport and Smith, Science 2010

Page 24: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 25: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 26: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Risk ratio = 1.9

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 27: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Risk ratio = 1.9(1.9 = 2.7% / 1.5%)

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 28: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Prenatal SSRI absent

1.5%

Risk ratio = 1.9

Prenatal SSRI present

2.7%

(1.9 = 2.7% / 1.5%)

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 29: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Prenatal SSRI absent

1.5%

Risk ratio = 1.9

Prenatal SSRI present

2.7%

1.2% absolute differencein risk

(1.9 = 2.7% / 1.5%)

③ The amount of increased risk any one risk environmental factor conveys to the individual is likely quite small

Page 30: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

④ However, the overall impact in the population can be quite large

Page 31: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

④ However, the overall impact in the population can be quite large

Page 32: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Risk ratio = 2.3 for each standard deviation of PM2.5

④ However, the overall impact in the population can be quite large

Page 33: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Risk ratio = 2.3 for each standard deviation of PM2.5

(2.3 = 3.5% / 1.5%)

④ However, the overall impact in the population can be quite large

Page 34: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

One SD belowthe mean

1.5%

Risk ratio = 2.3 for each standard deviation of PM2.5

One SD abovethe mean

3.5%

(2.3 = 3.5% / 1.5%)

④ However, the overall impact in the population can be quite large

Page 35: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

One SD belowthe mean

1.5%

Risk ratio = 2.3 for each standard deviation of PM2.5

One SD abovethe mean

3.5%

2% absolute differencein risk

(2.3 = 3.5% / 1.5%)

④ However, the overall impact in the population can be quite large

Page 36: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

④ However, the overall impact in the population can be quite large

Page 37: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

ASDprevalence

8.5%

ASDprevalence

0.1%

Risk ratio = 2.3 for each standard deviation of PM2.5

④ However, the overall impact in the population can be quite large

Page 38: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

④ However, the overall impact in the population can be quite large

Page 39: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

④ However, the overall impact in the population can be quite large

Page 40: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

Population ASD prevalence down from 1.5% to 1.4% (3% reduction in ASD cases in the population overall)

④ However, the overall impact in the population can be quite large

Page 41: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

④ However, the overall impact in the population can be quite large

Page 42: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

④ However, the overall impact in the population can be quite large

Page 43: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Births categorized by amount of prenatal exposure to air pollution (PM2.5)

Population ASD prevalence down from 1.5% to 0.8% (47% reduction in ASD cases in the population)

④ However, the overall impact in the population can be quite large

Page 44: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute
Page 45: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

Specific environmental risk factors with supporting evidence under study now

• Parental age• Pre-, peri-, and neonatal

complications– Low birth weight / SGA– Infection

• Prenatal medication use• Short interpregnancy interval• Prenatal (preconception) nutrition

– Folate • Prenatal (preconception) air

pollution• Endocrine disrupting chemicals

Page 46: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute
Page 47: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

www.prhe.ucsf.edu/info

Page 48: Four things you should know about environmental autism ...spark-sf.s3.amazonaws.com/webinar/...the_environment_webinar_sli… · Craig Newschaffer. Director, AJ Drexel Autism Institute

www.drexel.edu/[email protected]

QUESTIONS?