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Familial confounding of the association between maternal smoking during pregnancy and internalizing disorders in offspring

  • S. M. Meier (a1) (a2) (a3), K. J. Plessen (a2) (a3) (a4), F. Verhulst (a5) (a4), O. Mors (a6), P. B. Mortensen (a1) (a2) (a7), C. B. Pedersen (a1) (a2) (a7) and E. Agerbo (a1) (a2) (a7)...

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.


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.


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).


The results suggest that familial background factors account for the association between MSDP and severe internalizing disorders not the specific exposure to MSDP.

Corresponding author
*Address for correspondence: Dr S. M. Meier, National Centre for Register-Based Research, Aarhus University, Fuglesangs Allé 4, 8210 Aarhus V, Denmark. (Email:
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