Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence

A Nationwide Danish Study

Cecilie N. Lydholm, Ole Köhler-Forsberg, Merete Nordentoft, Robert H Yolken, Preben B. Mortensen, Liselotte Petersen, Michael E. Benros

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBiological Psychiatry
DOIs
StateAccepted/In press - Jan 1 2018

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Mental Disorders
Pregnancy
Mothers
Infection
Anti-Infective Agents
Confidence Intervals
Cross Infection
Schizophrenia
Cohort Studies
Regression Analysis

Keywords

  • Adolescent psychiatry
  • Child psychiatry
  • Inflammation
  • Parental infections
  • Pregnancy
  • Prenatal infections

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence : A Nationwide Danish Study. / Lydholm, Cecilie N.; Köhler-Forsberg, Ole; Nordentoft, Merete; Yolken, Robert H; Mortensen, Preben B.; Petersen, Liselotte; Benros, Michael E.

In: Biological Psychiatry, 01.01.2018.

Research output: Contribution to journalArticle

Lydholm, Cecilie N. ; Köhler-Forsberg, Ole ; Nordentoft, Merete ; Yolken, Robert H ; Mortensen, Preben B. ; Petersen, Liselotte ; Benros, Michael E. / Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence : A Nationwide Danish Study. In: Biological Psychiatry. 2018.
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title = "Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence: A Nationwide Danish Study",
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.",
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T1 - Parental Infections Before, During, and After Pregnancy as Risk Factors for Mental Disorders in Childhood and Adolescence

T2 - A Nationwide Danish Study

AU - Lydholm, Cecilie N.

AU - Köhler-Forsberg, Ole

AU - Nordentoft, Merete

AU - Yolken, Robert H

AU - Mortensen, Preben B.

AU - Petersen, Liselotte

AU - Benros, Michael E.

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Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - Child psychiatry

KW - Inflammation

KW - Parental infections

KW - Pregnancy

KW - Prenatal infections

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