Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring.

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  • Additional Information
    • Source:
      Publisher: American Medical Association Country of Publication: United States NLM ID: 101589550 Publication Model: Print Cited Medium: Internet ISSN: 2168-6238 (Electronic) Linking ISSN: 2168622X NLM ISO Abbreviation: JAMA Psychiatry Subsets: MEDLINE
    • Publication Information:
      Original Publication: Chicago, IL : American Medical Association, [2013]-
    • Subject Terms:
      Mental Disorders/*epidemiology ; Mental Disorders/*etiology ; Prenatal Exposure Delayed Effects/*epidemiology ; Smoking/*adverse effects ; Smoking/*epidemiology; Causality ; Cohort Studies ; Cross-Sectional Studies ; Female ; Gene-Environment Interaction ; Humans ; Male ; Mental Disorders/genetics ; Pregnancy ; Registries/statistics & numerical data ; Risk ; Statistics as Topic ; Sweden
    • Abstract:
      Importance: Several recent population-based studies have linked exposure to maternal smoking during pregnancy to increased risk of severe mental illness in offspring (eg, bipolar disorder, schizophrenia). It is not yet clear, however, whether this association results from causal teratogenic effects or from confounding influences shared by smoking and severe mental illness.
      Objective: To examine the association between smoking during pregnancy and severe mental illness in offspring, adjusting for measured covariates and unmeasured confounding using family-based designs.
      Design, Setting, and Participants: This study analyzed population register data through December 31, 2013, for a cohort of 1 680 219 individuals born in Sweden from January 1, 1983, to December 31, 2001. Associations between smoking during pregnancy and severe mental illness in offspring were estimated with adjustment for measured covariates. Cousins and siblings who were discordant on smoking during pregnancy and severe mental illness were then compared, which helped to account for unmeasured genetic and environmental confounding by design.
      Exposures: Maternal self-reported smoking during pregnancy, obtained from antenatal visits.
      Main Outcomes and Measures: Severe mental illness, with clinical diagnosis obtained from inpatient and outpatient visits and defined using International Classification of Diseases codes for bipolar disorder and schizophrenia spectrum disorders.
      Results: Of the 1 680 219 offspring included in the analysis, 816 775 (48.61%) were female. At the population level, offspring exposed to moderate and high levels of smoking during pregnancy had greater severe mental illness rates than did unexposed offspring (moderate smoking during pregnancy: hazard ratio [HR], 1.25; 95% CI, 1.19-1.30; high smoking during pregnancy: HR, 1.51; 95% CI, 1.44-1.59). These associations decreased in strength with increasing statistical and methodologic controls for familial confounding. In sibling comparisons with within-family covariates, associations were substantially weaker and nonsignificant (moderate smoking during pregnancy: HR, 1.09; 95% CI, 0.94-1.26; high smoking during pregnancy: HR, 1.14; 95% CI, 0.96-1.35). The pattern of associations was consistent across subsets of severe mental illness disorders and was supported by further sensitivity analyses.
      Conclusions and Relevance: This population- and family-based study failed to find support for a causal effect of smoking during pregnancy on risk of severe mental illness in offspring. Rather, these results suggest that much of the observed population-level association can be explained by measured and unmeasured factors shared by siblings.
    • Comments:
      Comment in: JAMA Psychiatry. 2017 Jun 1;74(6):561-562. (PMID: 28467524)
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    • Grant Information:
      K99 DA040727 United States DA NIDA NIH HHS; R01 MH102221 United States MH NIMH NIH HHS
    • Publication Date:
      Date Created: 20170504 Date Completed: 20170619 Latest Revision: 20190204
    • Publication Date:
      20231215
    • Accession Number:
      PMC5539841
    • Accession Number:
      10.1001/jamapsychiatry.2017.0456
    • Accession Number:
      28467540