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Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure.

ABSTRACT: To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms.Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control (n?=?6484) and a Mendelian randomization analysis (n?=?1020), using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy.A longitudinal birth cohort in South West England.Participants of the Avon Longitudinal Study of Parents and Children (ALSPAC).Smoking status during pregnancy was self-reported by mother and partner in questionnaires administered at pregnancy. Latent classes of offspring smoking initiation (non-smokers, experimenters, late-onset regular smokers and early-onset regular smokers) were previously developed from questionnaires administered at 14-16 years. A genetic variant, rs1051730, was genotyped in the mothers.Both mother and partner smoking were similarly positively associated with offspring smoking initiation classes, even after adjustment for confounders. Odds ratios (OR) [95% confidence interval (CI)] for class membership compared with non-smokers were: experimenters: mother OR?=?1.33 (95% CI?=?1.06, 1.67), partner OR?=?1.28 (95% CI?=?1.06, 1.55), late-onset regular smokers: mother OR?=?1.80 (95% CI?=?1.43, 2.26), partner OR?=?1.86 (95% CI?=?1.52, 2.28) and early-onset regular smokers: mother OR?=?2.89 (95% CI?=?2.12, 3.94), partner OR?=?2.50 (95% CI?=?1.85, 3.37). There was no clear evidence for a dose-response effect of either mother or partner smoking heaviness on class membership. Maternal rs1051730 genotype was not clearly associated with offspring smoking initiation class in pre-pregnancy smokers (P?=?0.35).The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms.

SUBMITTER: Taylor AE

PROVIDER: S-EPMC4114534 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure.

Taylor Amy E AE Howe Laura D LD Heron Jon E JE Ware Jennifer J JJ Hickman Matthew M Munafò Marcus R MR

Addiction (Abingdon, England) 20140317 6

<h4>Aims</h4>To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms.<h4>Design</h4>Comparison of associations of maternal and partner smoking behaviour during pregnancy with offspring smoking initiation using partner smoking as a negative control (n = 6484) and a Mendelian randomization analysis (n = 1020), using a genetic variant in the mothers as a proxy for smoking cessation during pregnancy.<h4>Setting</h4> ...[more]

PMID: 24521169

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Project description:ImportanceSeveral 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.ObjectiveTo 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 participantsThis 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.ExposuresMaternal self-reported smoking during pregnancy, obtained from antenatal visits.Main outcomes and measuresSevere 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.ResultsOf 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 relevanceThis 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.

Project description: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.

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Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure.

Publications

Maternal smoking during pregnancy and offspring smoking initiation: assessing the role of intrauterine exposure.

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