Background: Inflammation is strongly associated with premature birth and neonatal morbidities. Increases in infant haptoglobin (Hp&HpRP) and IL-6 levels are indicators of intra-amniotic inflammation (IAI) and have been linked to poor neonatal outcomes. Inflammation causes epigenetic changes, specifically suppression of miR-29 expression. The current study sought to determine whether miR-29b levels in cord blood or neonatal venous blood are associated with IAI, identified by elevated IL-6 and haptoglobin, and subsequent clinical morbidities in the infant. Methods: We tested 92 cord blood samples from premature newborns and 18 venous blood samples at 36 weeks corrected gestational age. MiR-29b, haptoglobin (Hp&HpRP), and IL-6 were measured by PCR and ELISA respectively. Results: Decreased levels of miR-29b were observed in infants exposed to IAI with elevated Hp&HpRP and IL-6 levels and in infants delivered by spontaneous preterm birth. Lower miR-29 levels were also observed in women diagnosed with histological chorioamnionitis or funisitis and in infants with cerebral palsy. Higher levels of miR-29 were measured in infants small for gestational age (SGA) and in venous samples from older infants. Conclusion: MiR-29 may be an additional biomarker of IAI and a potential therapeutic target for treating poor newborn outcomes resulting from antenatal exposure to IAI.

BackgroundPrevious reports have identified decreases in miR‐29b levels in preterm infants that go on to develop bronchopulmonary dysplasia (BPD). The cause of depressed miR‐29b levels is unknown but may reflect an adverse maternal and/or intrauterine environment that led to preterm birth. This study was designed to investigate relationships between antenatal circumstances related to preterm birth and cord blood levels of miR29b.MethodsWe analyzed 127 cord blood collected from consecutive deliveries (n=114) of liveborn infants born ≤30 weeks gestation (median 27.4 weeks: IQR [25.6–29.0]). Data on maternal co‐morbidities, antecendants to preterm birth (e.g., preeclampsia, fetal growth restriction, placental inflammation) were collected prospectively. miR‐29b levels were measured using RT‐PCR and normalized to expression of SP2. Data were analyzed for correlations by Spearman's correlation coefficient or Generalizing Estimating Equations (GEE) for mixed models controlling for twins.ResultsPreliminary results indicate that miR‐29b levels were correlated to umbilical funisitis (p=0.038). Regression analysis revealed miR‐29b is associated with intrauterine growth retardation (p=0.011) and pre‐term labor (p=0.007).ConclusionsmiR‐29b levels are associated with fetal inflammation and poor fetal growth. Maternal health is also related to fetal inflammation and further analyses of the clinical data is likely to reveal new correlations.Support or Funding InformationNIH NICHD R01HD088033This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.