DNA methylation at imprint regulatory regions in preterm birth and infection

OBJECTIVE: To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis). STUDY DESIGN: Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status. RESULTS: DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05. CONCLUSION: Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.