Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a blinding condition affecting preterm infants, is an interruption of retinal vascular maturation that is incomplete when born preterm. Although ROP demonstrates delayed onset following preterm birth, representing a window for therapeutic intervention, we cannot cure or prevent this disease. The in utero environment, including placental function, is increasingly recognized for contributions to preterm infant disease risk. Herein, we identify a protective association between acute placental inflammation and preterm infant ROP development using logistic regression, with the most significant association found for infants without gestational exposure to maternal preeclampsia and those with earlier preterm birth. Expression analysis of proteins with described ROP risk associations demonstrates significantly decreased placental HTRA-1 and fatty acid binding protein 4 protein expression for infants with acute placental inflammation compared with those without. Within the postnatal peripheral circulation, HTRA-1 and vascular endothelial growth factor-A demonstrate inverse longitudinal trends for infants born in the presence compared with absence of acute placental inflammation. An agnostic approach, including whole transcriptome and differential methylation placental analysis, further identifies novel mediators and pathways that may underly protection. Taken together, these data build on emerging literature showing a protective association between acute placental inflammation and ROP development and identify novel mechanisms that may inform postnatal risk associations in preterm infants.