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

AIMS: To assess whether associations between maternal smoking during pregnancy and offspring smoking initiation are due to intrauterine mechanisms. DESIGN: 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. SETTING: A longitudinal birth cohort in South West England. PARTICIPANTS: Participants of the Avon Longitudinal Study of Parents and Children (ALSPAC). MEASUREMENTS: 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. FINDINGS: 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). CONCLUSION: The association between smoking during pregnancy and offspring smoking initiation does not appear to operate through intrauterine mechanisms.