Placental methylation and pro-inflammatory protein levels in cord blood

Introduction: The 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 proinflammatory proteins in cord blood. Methods: A 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 alpha, intercellular adhesion molecule 1, serum amyloid A, and C-reactive protein. Results: We identified differential placental DNA methylation of three loci in the HIVEP3 gene shore region that were associated with TNF alpha protein levels in cord blood. TNF alpha 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. Conclusions: Our 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.