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Maternal smoking during pregnancy and fractures in offspring: national register based sibling comparison study.

ABSTRACT: OBJECTIVE:To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN:National register based birth cohort study with a sibling comparison design. SETTING:Sweden. PARTICIPANTS:1?680?307 people born in Sweden between 1983 and 2000 to women who smoked (n=377?367, 22.5%) and did not smoke (n=1?302?940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE:Fractures by attained age up to 32 years. RESULTS:During a median follow-up of 21.1 years, 377?970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ?10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION:Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.

SUBMITTER: Brand JS

PROVIDER: S-EPMC7190030 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Maternal smoking during pregnancy and fractures in offspring: national register based sibling comparison study.

Brand Judith S JS Hiyoshi Ayako A Cao Yang Y Lawlor Deborah A DA Cnattingius Sven S Montgomery Scott S

BMJ (Clinical research ed.) 20200129

<h4>Objective</h4>To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life.<h4>Design</h4>National register based birth cohort study with a sibling comparison design.<h4>Setting</h4>Sweden.<h4>Participants</h4>1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014.<h4>Main outcome measure</h4>Fractur ...[more]

PMID: 31996343

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Project description: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.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.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.Maternal self-reported smoking during pregnancy, obtained from antenatal visits.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.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.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.

Dataset Information

Maternal smoking during pregnancy and fractures in offspring: national register based sibling comparison study.

Publications

Maternal smoking during pregnancy and fractures in offspring: national register based sibling comparison study.

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