Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood

Through the Pregnancy And Childhood Epigenetics Consortium (PACE), we conducted a meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation. Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements were available in a few studies and provided objective data on maternal exposure to secondhand smoke (SHS) and smoking during pregnancy. Differential DNA methylation in newborns were evaluated in relation to maternal sustained smoking, maternal SHS exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, and paternal quitting before pregnancy. For CpGs on the 450K, maternal sustained smoking was associated with differential DNA methylation (false discovery rate [FDR] <0.05) at 8,862 CpGs. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. cg24805739 (MED13L) was associated with paternal former smoking. For CpGs unique to the EPIC array, differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs).