한빛사 논문
Jong Yeob Kima,†, Min Ji Son MDa,†, Chei Yun Son BAb,†, Joaquim Radua MDc,d,e,f, Michael Eisenhut MDg, Florence Gressier MDh, Ai Koyanagi MDi,j,k, Andre F Carvalho MDk,l, Brendon Stubbs PhDm,n, Marco Solmi MDo,p, Theodor B Rais MDq, Keum Hwa Lee MDr,s, Andreas Kronbichler PhDt, Elena Dragioti PhDu, Jae Il Shin MDr,s,*, Paolo Fusar-Poli MDp,v,*
a Yonsei University College of Medicine, Seoul, Republic of Korea
b Department of Psychological & Brain Sciences, Washington University in St. Louis, MO, USA
c Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
d FIDMAG Germanes Hospitalaries, CIBERSAM, Barcelona, Spain
e Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
f Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
g Department of Pediatrics, Luton & Dunstable University Hospital NHS Foundation Trust, Luton, UK
h CESP, Inserm UMR1178, Department of Psychiatry, Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Le Kremlin Bicêtre, France
i Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, Barcelona, Spain
j Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain
k Centre for Addiction & Mental Health, Toronto, ON, Canada
l Department of Psychiatry, University of Toronto, Toronto, ON, Canada
m Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK
n Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
o Department of Neurosciences and Neurosciences Center, University of Padua, Padua, Italy
p Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
q Department of Psychiatry, University of Toledo Medical Center, Toledo, Ohio, USA
r Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea
s Department of Pediatrics, Severance Children's Hospital, Seoul, South Korea
t Department of Internal Medicine IV, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
u Pain and Rehabilitation center and Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences University of Linköping, Linköping, Sweden
v OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK
†Contributed equally
*Correspondence
Abstract
Background
Numerous studies have identified potential risk factors and biomarkers for autism spectrum disorder. We aimed to study the strength and validity of the suggested environmental risk factors or biomarkers of autism spectrum disorder.
Methods
We did an umbrella review and systematically appraised the relevant meta-analyses of observational studies. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for papers published between database inception and Oct 17, 2018, and screened the reference list of relevant articles. We obtained the summary effect, 95% CI, heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We did analyses under credibility ceilings. This review is registered with PROSPERO, number CRD42018091704.
Findings
46 eligible articles yielded data on 67 environmental risk factors (544 212 cases, 81 708 787 individuals) and 52 biomarkers (15 614 cases, 15 433 controls). Evidence of association was convincing for maternal age of 35 years or over (relative risk [RR] 1·31, 95% CI 1·18–1·45), maternal chronic hypertension (odds ratio [OR] 1·48, 1·29–1·70), maternal gestational hypertension (OR 1·37, 1·21–1·54), maternal overweight before or during pregnancy (RR 1·28, 1·19–1·36), pre-eclampsia (RR 1·32, 1·20–1·45), prepregnancy maternal antidepressant use (RR 1·48, 1·29–1·71), and maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy (OR 1·84, 1·60–2·11). Only two associations, maternal overweight before or during pregnancy and SSRI use during pregnancy, retained their high level of evidence under subset sensitivity analyses. Evidence from biomarkers was scarce, being supported by p values close to the significance threshold and too few cases.
Interpretation
Convincing evidence suggests that maternal factors, such as age and features of metabolic syndrome, are associated with risk of autism spectrum disorder. Although SSRI use during pregnancy was also associated with such risk when exposed and non-exposed groups were compared, this association could be affected by other confounding factors, considering that prepregnancy maternal antidepressant use was also convincingly associated with higher risk of autism spectrum disorder. Findings from previous studies suggest that one possible confounding factor is underlying maternal psychiatric disorders.
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