title: Familial confounding of the association between maternal smoking during pregnancy and internalizing disorders in offspring.
abstract: BACKGROUND
  Maternal smoking has consistently been associated with multiple adverse childhood outcomes including externalizing disorders. In contrast the association between maternal smoking during pregnancy (MSDP) and internalizing (anxiety and depressive) disorders in offspring has received less investigation.
  
  
  METHODS
  We conducted a nationwide cohort study including 957635 individuals born in Denmark between 1991 and 2007. Data on MSDP and diagnoses of depression or anxiety disorders were derived from national registers and patients were followed up from the age of 5 years to the end of 2012. Hazard rate ratios (HRRs) were estimated using stratified Cox regression models. Sibling data were used to disentangle individual- and familial-level effects of MSDP and to control for unmeasured familial confounding.
  
  
  RESULTS
  At the population level, offspring exposed to MSDP were at increased risk for both severe depression [HRR 1.29, 95% confidence interval (CI) 1.22-1.36] and severe anxiety disorders (HRR 1.26, 95% CI 1.20-1.32) even when controlling for maternal and paternal traits. However, there was no association between MSDP and internalizing disorders when controlling for the mother's propensity for MSDP (depression: HRR 1.11, 95% CI 0.94-1.30; anxiety disorders: HRR 0.94, 95% CI 0.80-1.11) or comparing differentially exposed siblings (depression: HRR 1.18, 95% CI 0.75-1.89; anxiety disorders: HRR 0.87, 95% CI 0.55-1.36).
  
  
  CONCLUSIONS
  The results suggest that familial background factors account for the association between MSDP and severe internalizing disorders not the specific exposure to MSDP.
authors.affiliation: National Centre for Register-Based Research NCRR, Aarhus University, Aarhus V,Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Denmark.|Child and Adolescent Mental Health Centre - Mental Health Services Capital Region, Copenhagen Region,Denmark.
authors.forename: S M
authors.initials: SM
authors.lastname: Meier
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Denmark.|Child and Adolescent Mental Health Centre - Mental Health Services Capital Region, Copenhagen Region,Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: K J
authors.initials: KJ
authors.lastname: Plessen
authors.affiliation: Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Verhulst
authors.affiliation: Psychosis Research Unit, Aarhus University Hospital, Risskov,Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.affiliation: National Centre for Register-Based Research NCRR, Aarhus University, Aarhus V,Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Denmark.|CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus V, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: National Centre for Register-Based Research NCRR, Aarhus University, Aarhus V,Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Denmark.|CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus V, Denmark.
authors.forename: C B
authors.initials: CB
authors.lastname: Pedersen
authors.affiliation: National Centre for Register-Based Research NCRR, Aarhus University, Aarhus V,Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research iPSYCH, Denmark.|CIRRAU - Centre for Integrated Register-based Research, Aarhus University, Aarhus V, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Agerbo
keywords: Anxiety disorders; depression; familial confounding; maternal smoking; sibling