The British Journal of Psychiatry (2009) 195: 7-14. doi: 10.1192/bjp.bp.108.051672
© 2009 The Royal College of Psychiatrists
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REVIEW ARTICLES

Prenatal risk factors for autism: comprehensive meta-analysis

Hannah Gardener, ScD

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts

Donna Spiegelman, ScD

Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts

Stephen L. Buka, ScD

Department of Community Health, Brown University, Providence, Rhode Island, USA

Correspondence: Hannah Gardener, Department of Neurology, University of Miami Miller School of Medicine, Post Office Box 016960 (M712), Miami, FL 33101, USA. Email: hgardener{at}med.miami.edu

Declaration of interest

None.

Funding

H.G. received a National Research Service Award grant from the Training Program in Psychiatric Epidemiology and Biostatistics (T32 MH17119). Partial funding was provided by the Stanley Medical Research Institute.

Background

The aetiology of autism is unknown, although prenatal exposures have been the focus of epidemiological research for over 40 years.

Aims

To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.

Method

PubMed, Embase and PsycINFO databases were searched for epidemiological studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.

Results

Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born v. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, pre-eclampsia and swelling.

Conclusions

There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.