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Original Investigation
May 3, 2017

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

Author Affiliations
  • 1Department of Psychological and Brain Sciences, Indiana University, Bloomington
  • 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 3Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
  • 4School of Medical Sciences, Örebro University, Örebro, Sweden
JAMA Psychiatry. Published online May 3, 2017. doi:10.1001/jamapsychiatry.2017.0456
Key Points

Question  Does exposure to maternal smoking during pregnancy increase the risk of severe mental illness in offspring?

Findings  In a population-based cohort of 1.7 million Swedish offspring, maternal smoking during pregnancy was associated with an increased risk of severe mental illness in offspring. However, sibling comparisons, which ruled out all genetic and environmental confounders that make siblings similar, revealed much weaker and statistically nonsignificant associations.

Meaning  This study suggests that much of the association between smoking during pregnancy and severe mental illness in offspring is likely explained by familial confounding rather than by causal teratogenic effects.

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.

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