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Association Between Maternal Smoking During Pregnancy and Severe Mental Illness in Offspring
Department of Psychological and Brain Sciences, Indiana University, Bloomington IN, United States.
Department of Psychological and Brain Sciences, Indiana University, Bloomington IN, United States.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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2017 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 74, no 6, 589-596 p.Article 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, 589-596 p.
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: 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

Available from: 2017-07-26 Created: 2017-07-26 Last updated: 2017-09-18Bibliographically approved

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CiteExportLink to record
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Citation style
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