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A Longitudinal Study of a National Birth Cohort

Christina Dalman, MD; Peter Allebeck, MD, PhD; Johan Cullberg, MD; Charlotta Grunewald, MD, PhD; Max Köster

Arch Gen Psychiatry. 1999;56:234-240.

Background  Numerous epidemiological studies found an increased risk of schizophrenia among persons exposed to various obstetric complications. The underlying mechansims are unknown.

Objective  To study specific risk factors, as well as sets of risk factors, representing 3 different etiologic mechanisms: (1) malnutrition during fetal life; (2) extreme prematurity; and (3) hypoxia or ischemia.

Methods  In this longitudinal cohort study, information in the National Birth Register was linked to the National Inpatient Register. We followed up 507,516 children born between 1973 and 1977 with regard to a diagnosis of schizophrenia between 1987 and 1995 (238 cases). By record linkage, we also had access to data on psychiatric illness in the mother. Occurrence of schizophrenia was measured by the Mantel-Haenszel test and logistic regression.

Results  A number of specific risk factors were associated with an increased risk of schizophrenia. The relative risk (95% confidence interval) for preeclampsia was 2.5 (1.4-4.5); vacuum extraction, 1.7 (1.1-2.6); and malformations, 2.4 (1.2-5.1). In logistic regression models, we found that indicators of all 3 etiologic mechanisms were associated with increased point estimates of schizophrenia, although at lower risk levels. Preeclampsia, an indicator of fetal malnutrition, was the only risk factor with statistically significant increased risk after control for all potentially confounding factors.

Conclusion  This study supports the theory of an association between obstetric complications and schizophrenia. Although preeclampsia was the strongest individual risk factor, there was evidence of increased risk associated with all 3 etiologic mechanisms.

From the Stockholm County Child and Adolescent Public Health Unit (Dr Dalman) and the Department of Obstetrics and Gynecology (Dr Grunewald), Huddinge University Hospital; the Center for Psychosis Research, South Stockholm Health Authority (Dr Cullberg); and the Center for Epidemiology, National Board of Health and Welfare (Mr Köster), Stockholm, Sweden; and the Department of Social Medicine, Vasa Hospital, University of Gothenburg (Dr Allebeck), Gothenburg, Sweden.

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