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April 2007

Prenatal and Perinatal Risk Factors for Autism: A Review and Integration of Findings

Author Affiliations

Author Affiliations: Department of Psychiatry, Mount Sinai School of Medicine (Drs Kolevzon and Reichenberg), Department of Epidemiology, Mailman School of Public Health, Columbia University (Dr Gross), and Department of Psychiatry, College of Physicians and Surgeons, Columbia University (Dr Gross), New York, NY; Unit of Mental Health Epidemiology, The Gertner Institute of Epidemiology and Health Policy Research, Tel Hashomer, Israel (Dr Gross); and Department of Psychological Medicine, Institute of Psychiatry, King's College, London, England (Dr Reichenberg).

Arch Pediatr Adolesc Med. 2007;161(4):326-333. doi:10.1001/archpedi.161.4.326

Objective  To review the evidence for the presence of prenatal and perinatal factors that affect the risk of autism and autism spectrum disorders.

Data Sources  Relevant articles were identified by searching MEDLINE, screening reference lists of original studies, and searching major journals likely to publish epidemiological studies on the topic.

Study Selection  For inclusion in this review, studies required (1) a well-defined sample of cases drawn from population-based registers or cohorts; (2) standardized, prospectively collected obstetric information from birth records or registers; (3) comparison subjects drawn from the general population with information on obstetric complications collected from the same source; and (4) a standardized format for presentation of data, allowing for comparisons among studies.

Main Exposures  Parental characteristics and obstetric complications.

Main Outcome Measures  Rates of autism and autism spectrum disorders.

Results  Seven epidemiological studies were identified that fulfilled inclusion criteria. The parental characteristics associated with an increased risk of autism and autism spectrum disorders included advanced maternal age, advanced paternal age, and maternal place of birth outside Europe or North America. The obstetric conditions that emerged as significant fell into 2 categories: (1) birth weight and duration of gestation and (2) intrapartum hypoxia.

Conclusions  Evidence to suggest that parental age and obstetric conditions are associated with an increased risk of autism and autism spectrum disorders is accumulating. Although not proven as independent risk factors for autism, these variables should be examined in future studies that use large, population-based birth cohorts with precise assessments of exposures and potential confounders.