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Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia
Suggestions From a Study of Sibship Characteristics and Influenza Prevalence
Tine Westergaard, MD;
Preben B. Mortensen, MD, PhD;
Carsten B. Pedersen, MSc;
Jan Wohlfahrt, MSc;
Mads Melbye, MD, DMSc
Arch Gen Psychiatry. 1999;56:993-998.
Background It has been proposed that infections, perhaps prenatal exposure to the influenza virus, might increase the risk of schizophrenia. To address this hypothesis, we studied the possible influence on schizophrenia risk of sibship characteristics and ecological influenza prevalence data. Birth order and influenza prevalence were used as proxy measures for exposure to prenatal infection, and sibship size and interval to siblings were used as proxy measures for exposure to common childhood infections.
Methods We established a population-based cohort of 1,746,366 persons whose mothers were Danish-born women born since 1935 by using data from the Civil Registration System. Schizophrenia in cohort members (n=2669) and their parents was identified by linkage with the Danish Psychiatric Case Register. Birth order, sibship size, and interval to siblings were calculated for each cohort member based on person-identifiable information on all siblings. The number of notifications of influenza per month in Denmark was obtained from the National Board of Health and Statens Serum Institut.
Results There was no association between birth order and schizophrenia risk or between schizophrenia risk and influenza prevalence during any month of prenatal life. Coming from a large sibship was associated with an increased schizophrenia risk. The relative risks were 1.26 (95% confidence interval [CI], 1.11-1.44) and 1.46 (95% CI, 1.22-1.75) for sibships of 4 and 5 or more, respectively, vs a sibship of 2. Short interval (<2 years) to the nearest older sibling and nearest younger sibling was associated with a risk of 1.22 (95% CI, 1.05-1.38) and 1.15 (95% CI, 1.03-1.28), respectively, compared with longer intervals.
Conclusions Our findings do not support the hypothesis that schizophrenia is associated with prenatal exposure to common infections or influenza. However, they are compatible with the hypothesis that environmental exposure, perhaps to common infections in childhood, may be a risk factor, although other explanations are also possible.
From the Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark (Drs Westergaard and Melbye and Messrs Pedersen and Wohlfahrt); and the Department of Psychiatric Demography, Institute for Basic Psychiatric Research, Psychiatric Hospital, Aarhus, Denmark (Dr Mortensen).
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