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Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence: A Nationwide Danish Study

  • Cecilie N. Lydholm
    Correspondence
    Address correspondence to Cecilie N. Lydholm, B.Sc., Mental Health Centre Copenhagen, Copenhagen University Hospital, Gentofte Hospital, Kildegaardsvej 28, Entrance 15, 4th Floor, 2900 Hellerup, Denmark.
    Affiliations
    Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
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  • Ole Köhler-Forsberg
    Affiliations
    Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark

    Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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  • Merete Nordentoft
    Affiliations
    Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
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  • Robert H. Yolken
    Affiliations
    Stanley Division of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Preben B. Mortensen
    Affiliations
    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
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  • Author Footnotes
    ∗ LP and MEB contributed equally to this work as joint last authors.
    Liselotte Petersen
    Footnotes
    ∗ LP and MEB contributed equally to this work as joint last authors.
    Affiliations
    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
    Search for articles by this author
  • Author Footnotes
    ∗ LP and MEB contributed equally to this work as joint last authors.
    Michael E. Benros
    Footnotes
    ∗ LP and MEB contributed equally to this work as joint last authors.
    Affiliations
    Mental Health Centre Copenhagen, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University Hospital, Risskov, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
    Search for articles by this author
  • Author Footnotes
    ∗ LP and MEB contributed equally to this work as joint last authors.

      Abstract

      Background

      Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking.

      Methods

      A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis.

      Results

      Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval [CI], 1.06–1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98–1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14–1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95–1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001).

      Conclusions

      Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.

      Keywords

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