Abstract
BackgroundThe 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.MethodsThis was a 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.ResultsThose exposed to maternal smoking in pregnancy had increased odds of ID [odds ratio (OR) = 1.24, 95% confidence interval (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 in primary analyses.ConclusionsOur findings are consistent with a causal effect of maternal smoking in pregnancy on risk of offspring born SGA but not on risk of ID. We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for SGA.
Highlights
The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction
We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for small for gestational age (SGA)
Comparison of associations that are suspected to be the result of residual confounding with those that have a strong body of evidence for being causal can be useful for understanding the causal nature of the former association
Summary
The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. Three better quality studies not included in the review found an association between smoking in pregnancy and offspring risk of ID, but each suggested that this may be the result of residual confounding.[13,14,15] Further triangulation of evidence from different causal inference techniques is required to establish whether such an interpretation is likely.[16,17,18] In contrast, the association between smoking in pregnancy and offspring fetal growth restriction has strong evidence of being causal in nature, from complementary causal inference designs.[19,20,21] This latter association can be used as a positive control for smoking in pregnancy and offspring ID By this we mean that, using the same causal inference methods, if an association is found for fetal growth restriction but not ID this will support the interpretation that observational associations with ID are the result of residual confounding.If a causal effect of smoking in pregnancy on ID does exist, a crosscontext comparison between the associations of snus use and smoking in pregnancy with offspring ID can be used to investigate whether effects are the result of nicotine or of the combustible components of cigarette smoke. Smokeless tobacco that is increasingly being used as a smoking cessation aid in Sweden,[22,23] with some suggestion that it is more successful as an aid to stopping smoking than nicotine patches or gum.[24,25] Snus delivers nicotine in quantities that are comparable to cigarette smoke though with slower absorption and higher plasma nicotine concentration over an extended period.[22,26]
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