Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in OffspringShow others and affiliations
2017 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 74, no 6, p. 589-596Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
American Medical Association , 2017. Vol. 74, no 6, p. 589-596
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-58784DOI: 10.1001/jamapsychiatry.2017.0456ISI: 000402867200010PubMedID: 28467540Scopus ID: 2-s2.0-85020716305OAI: oai:DiVA.org:oru-58784DiVA, id: diva2:1128564
Funder
Swedish Research Council, 2013-2280 2011-2492Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-1678
Note
Funding Agencies:
National Institute of Mental Health R01MH102221
National Institute on Drug Abuse K99DA040727
Indiana Clinical and Translational Sciences Institute: Pediatric Project Development Team
Swedish Initiative for Research on Microdata in the Social and Medical Sciences 340-2013-5867
2017-07-262017-07-262017-09-18Bibliographically approved