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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.

Abstract

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 1746366 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.

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  • Authors+Show Affiliations

    ,

    Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen. twe@ssi.dk

    , , ,

    Source

    Archives of general psychiatry 56:11 1999 Nov pg 993-8

    MeSH

    Adult
    Birth Order
    Child
    Denmark
    Family Characteristics
    Female
    Humans
    Infection
    Influenza, Human
    Male
    Pregnancy
    Prenatal Exposure Delayed Effects
    Prevalence
    Registries
    Risk
    Risk Factors
    Schizophrenia

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10565498

    Citation

    Westergaard, T, et al. "Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia: Suggestions From a Study of Sibship Characteristics and Influenza Prevalence." Archives of General Psychiatry, vol. 56, no. 11, 1999, pp. 993-8.
    Westergaard T, Mortensen PB, Pedersen CB, et al. Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence. Arch Gen Psychiatry. 1999;56(11):993-8.
    Westergaard, T., Mortensen, P. B., Pedersen, C. B., Wohlfahrt, J., & Melbye, M. (1999). Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence. Archives of General Psychiatry, 56(11), pp. 993-8.
    Westergaard T, et al. Exposure to Prenatal and Childhood Infections and the Risk of Schizophrenia: Suggestions From a Study of Sibship Characteristics and Influenza Prevalence. Arch Gen Psychiatry. 1999;56(11):993-8. PubMed PMID: 10565498.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Exposure to prenatal and childhood infections and the risk of schizophrenia: suggestions from a study of sibship characteristics and influenza prevalence. AU - Westergaard,T, AU - Mortensen,P B, AU - Pedersen,C B, AU - Wohlfahrt,J, AU - Melbye,M, PY - 1999/11/24/pubmed PY - 1999/11/24/medline PY - 1999/11/24/entrez SP - 993 EP - 8 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 56 IS - 11 N2 - 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 1746366 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. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/10565498/Exposure_to_prenatal_and_childhood_infections_and_the_risk_of_schizophrenia:_suggestions_from_a_study_of_sibship_characteristics_and_influenza_prevalence_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&amp;PAGE=linkout&amp;SEARCH=10565498.ui DB - PRIME DP - Unbound Medicine ER -