Maternal smoking and smokeless tobacco use during pregnancy and offspring development: Sibling analysis in an intergenerational Swedish cohort

Background: The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. As fetal growth and cognitive development may share similar confounding structures, comparison of the two associations may improve understanding of the causal nature of the association with ID. Furthermore, comparisons of smoking with smokeless tobacco use may aid identification of mechanisms of action.

Method: Cohort study of all Swedish births between 1999 and 2012 (n=1 070 013), with prospectively recorded data. We assessed the association between maternal smoking during pregnancy and offspring outcomes ID and born small for gestational age (SGA). Analyses were repeated for snus use in pregnancy. Using a sibling design, we estimated within-family effects that control for shared sibling characteristics.

Results: Those exposed to maternal smoking in pregnancy had increased odds of ID (OR=1.24, 95% CI: 1.16-1.33) and SGA (OR=2.19, 95% CI: 2.11-2.27) after confounder adjustment. Within-family effects were found for SGA (OR=1.44, 95% CI: 1.27-1.63) but not ID (OR=0.92, 95% CI: 0.74-1.14). For snus use, the results for ID were similar to smoking. We found increased odds of offspring SGA among mothers who used snus in pregnancy in sensitivity analyses but not primary analyses.

Conclusions: Our findings are consistent with a causal effect of maternal smoking in pregnancy on risk of offspring born SGA but not risk of ID. We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for SGA.