Evaluation of past smoking of mothers and DNA methylation in cord blood of infants

Background: Maternal smoking is related to multiple adverse health outcomes in children. We previously reported an association between maternal smoking during pregnancy and differential DNA methylation in newborn cord bloods for CpG sites (CpGs) in genes involved in the aryl hydrocarbon receptor signaling pathway and key developmental processes. However, it remains unclear whether these modifications to the infant epigenome reflect in utero exposures only or the inheritance of epigenetic marks from the mother. Aims: We evaluated the association between maternal smoking before or during pregnancy and DNA methylation for 21 CpGs previously identified as differentially methylated in response to maternal smoking in 1,047 newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Methods: Maternal self-report of smoking as well as maternal plasma cotinine measured during pregnancy were used to distinguish mothers into four groups (never smokers, former smokers, smokers who smoked during pregnancy but quit by 18 weeks, and active smokers throughout pregnancy). The association between smoking and methylation was assessed using linear regression. Results: Having a mother who formerly smoked was not associated with differential methylation in cord blood for any of the 21 CpGs (at FDR of 0.05). Quitting during pregnancy was also not significantly associated with differential methylation (at FDR of 0.05) although methylation differences were larger than those for former smokers compared to never smokers. Only active smoking throughout pregnancy was statistically significantly associated with differential methylation (at FDR of 0.05). Conclusions: Differential methylation in newborn cord blood at the 21 CpGs that we previously found to be related to maternal smoking in pregnancy was only observed where mothers smoked during pregnancy. These findings suggest that DNA methylation at these locations in the infant epigenome reflects in utero exposure rather than epigenetic inheritance of smoking-related modifications in the mother.