Maternal smoking and DNA methylation in newborns: In utero effect or epigenetic inheritance?

Publication Type:

Journal Article


Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (2014)


2014, May 2014, Public Health Sciences Division


Background: Maternal smoking in pregnancy is associated with adverse health outcomes in children, including cancers; underlying mechanisms may include epigenetic modifications. Using Illumina's 450K array, we previously identified differential DNA methylation related to maternal smoking during pregnancy at 26 CpG sites (CpGs) in 10 genes in newborn cord bloods from the Norwegian Mother and Child Cohort Study (MoBa). Whether these methylation signals in newborns reflect in utero exposure only or possibly epigenetic inheritance of smoking-related modifications is unclear. Methods: We therefore evaluated the impact of the timing of mother's smoking (before or during pregnancy using cotinine measured at 18 weeks gestation), the father's smoking before conception, and the grandmother's smoking during her pregnancy with the mother on methylation at these 26 CpGs in 1,042 MoBa newborns. We used robust linear regression, adjusting for covariates, applying Bonferroni correction. Results: The strongest and only statistically significant associations were observed for sustained smoking by the mother during pregnancy through at least gestational week 18 (p<1.6x10-5 for all 26 CpGs). We observed no statistically significant differential methylation due to smoking by the mother prior to pregnancy or that ceased by week 18, father's smoking before conception, or grandmother's smoking while pregnant with the mother. Conclusions: Differential methylation at these CpGs in newborns appears to reflect sustained in utero exposure rather than epigenetic inheritance. Impact: Smoking cessation in early pregnancy may negate effects on methylation. Analyses of maternal smoking during pregnancy and offspring health outcomes, including cancer, limited to ever smoking might miss true associations.