Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smokingduring pregnancy(MSDP) contributes to poor birth outcomes, in part through disrupted placentalfunctions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placentalDNA methylation ( DNAm) and between DNAmand birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placentalMSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placentalfunction. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placentalfunction and fetal growth.