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Environmental Risk Factors and Biomarkers for Autism Spectrum Disorder: An Umbrella Review of the Evidence

63 Pages Posted: 5 Feb 2019

See all articles by Jong Yeob Kim

Jong Yeob Kim

Yonsei University - College of Medicine

Min Ji Son

Yonsei University - College of Medicine

Chei Yun Son

Washington University in St. Louis

Joaquim Radua

University of London - Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab

Michael Eisenhut

Government of the United Kingdom - Luton and Dunstable University Hospital

Florence Gressier

Bicêtre University Hospital

Ai Koyanagi

University of Barcelona

Andre F. Carvalho

University of Toronto - Centre for Addiction and Mental Health (CAMH); University of Toronto - Department of Psychiatry

Brendon Stubbs

South London and Maudsley NHS Foundation Trust, Physiotherapy Department; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine

Marco Solmi

University of Padua - Neurosciences Department; University of Padua - Neuroscience Center; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab

Theodor B. Rais

University of Toledo

Keum Hwa Lee

Yonsei University - Department of Pediatrics

Andreas Kronbichler

Medical University of Innsbruck

Elena Dragioti

Linkoping University - Pain and Rehabilitation Center

Jae Il Shin

Yonsei University - Department of Pediatrics

Paolo Fusar-Poli

University of London - Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab; Government of the United Kingdom - OASIS Service; University of Pavia - Department of Brain and Behavioral Sciences

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Abstract

Background: Numerous studies have identified the potential risk factors and biomarkers for autism spectrum disorder (ASD). We aim to study the strength and validity of the suggested environmental risk factors or biomarkers of ASD.  

Methods: We conducted an umbrella review and systematically appraised the relevant meta-analyses of observational studies (PROSPERO registration: CRD42014010715). We searched PubMed from inception to 10/17/2018 and screened the reference list of relevant articles. We obtained the summary effect, 95% confidence interval (CI), heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We performed analyses under credibility ceilings.  

Findings: A total of 46 eligible articles yielded data on 67 environmental risk factors (cases=544212, population=81708787) and 52 biomarkers (cases=15614, controls=15417). Evidence of association was convincing for greater maternal age (RR=1·31, 95% CI=1·18 to 1·45), maternal chronic hypertension (OR=1·48, 95% CI=1·29 to 1·70), maternal gestational hypertension (OR=1·37, 95% CI=1·21 to 1·54), maternal overweight (RR=1·28, 95% CI=1·19 to 1·36), preeclampsia (RR=1·32, 95% CI=1·20 to 1·45), pre-pregnancy maternal antidepressant exposure (RR=1·48, 95% CI=1·29 to 1·71), and selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy (OR=1·84, 95% CI=1·60 to 2·11). Only two associations, maternal overweight and SSRI during pregnancy, retained high level of evidence under subgroup sensitivity analyses. Evidence from biomarkers was limited.  

Interpretation: Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome are associated with risk of ASD. SSRI use during pregnancy was also convincingly associated with risk of ASD, but confounding from underlying maternal psychiatric disorders is possible.  

Funding: None.  

Declaration of Interest: We declare no competing interests.

Ethical Approval: PROSPERO registration: CRD42014010715

Keywords: autism; risk factors; environment; epidemiology; metaanalysis; umbrella review

Suggested Citation

Kim, Jong Yeob and Son, Min Ji and Son, Chei Yun and Radua, Joaquim and Eisenhut, Michael and Gressier, Florence and Koyanagi, Ai and Carvalho, Andre F. and Stubbs, Brendon and Solmi, Marco and Rais, Theodor B. and Lee, Keum Hwa and Kronbichler, Andreas and Dragioti, Elena and Shin, Jae Il and Fusar-Poli, Paolo, Environmental Risk Factors and Biomarkers for Autism Spectrum Disorder: An Umbrella Review of the Evidence (January 30, 2019). Available at SSRN: https://ssrn.com/abstract=3327365

Jong Yeob Kim

Yonsei University - College of Medicine

Korea, Republic of (South Korea)

Min Ji Son

Yonsei University - College of Medicine

Korea, Republic of (South Korea)

Chei Yun Son

Washington University in St. Louis

One Brookings Drive
Campus Box 1208
Saint Louis, MO MO 63130-4899
United States

Joaquim Radua

University of London - Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab

London
United Kingdom

Michael Eisenhut

Government of the United Kingdom - Luton and Dunstable University Hospital

Luton
United Kingdom

Florence Gressier

Bicêtre University Hospital

Le Kremlin Bicêtre
France

Ai Koyanagi

University of Barcelona

Gran Via de les Corts Catalanes, 585
Barcelona, 08007
Spain

Andre F. Carvalho

University of Toronto - Centre for Addiction and Mental Health (CAMH)

1001 Queen Street West
Toronto, Ontario M6J 1H4
Canada

University of Toronto - Department of Psychiatry

Toronto
Canada

Brendon Stubbs

South London and Maudsley NHS Foundation Trust, Physiotherapy Department

London
United Kingdom

King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine

London
United Kingdom

Marco Solmi

University of Padua - Neurosciences Department

Padua
Italy

University of Padua - Neuroscience Center

Padua
Italy

King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab

London
United Kingdom

Theodor B. Rais

University of Toledo

Mail Stop 119, HH 3000
Toledo, OH 43606
United States

Keum Hwa Lee

Yonsei University - Department of Pediatrics

Seoul
Korea, Republic of (South Korea)

Andreas Kronbichler

Medical University of Innsbruck

Innrain 52
Christoph-Probst-Platz
Innsbruck, 6020
Austria

Elena Dragioti

Linkoping University - Pain and Rehabilitation Center

Linköping
Sweden

Jae Il Shin

Yonsei University - Department of Pediatrics ( email )

Seoul
Korea, Republic of (South Korea)

Paolo Fusar-Poli (Contact Author)

University of London - Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab ( email )

London
United Kingdom

Government of the United Kingdom - OASIS Service ( email )

London
United Kingdom

University of Pavia - Department of Brain and Behavioral Sciences ( email )

Pavia
Italy

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