IntroductionThe neonates’ inflammatory response may in part be shaped during development by the placental epigenome, but evidence is scarce. We investigated the association between placental DNA methylation and pro-inflammatory proteins in cord blood. MethodsA total of 249 mother-child dyads from the Harvard Epigenetic Birth Cohort were included in this study. Genome-wide methylation in placental DNA was assessed using the Illumina Human Methylation 450 Bead Chip array and verified by pyrosequencing. Cord blood inflammation markers assessed were interleukin-6, interleukin-8 and tumor necrosis factor α, intercellular adhesion molecule 1, serum amyloid A, and C-reactive protein. ResultsWe identified differential placental DNA methylation of three loci in the HIVEP3 gene shore region that were associated with TNFα protein levels in cord blood. TNFα levels were associated with mode of delivery, gestational age and birth order. Three other loci located in the open sea region of the BCL11B gene were associated with SAA protein levels in cord blood. SAA levels were associated with birthweight, gestational age, and infant sex. ConclusionsOur results suggest a potential role for HIVEP3 and BCL11B placental DNA methylation in the acute immune response of the neonate. These immune markers were correlated with several mother and child characteristics.