Abstract
Purpose :
The relationship between placental inflammation and retinopathy of prematurity (ROP) is debated. Clarity may provide clues to potential pathomechanisms influencing pre-clinical ROP risk.
Methods :
Acute placental inflammation for infants born prior to 32 weeks between 2010-2019 at one institution was characterized using gold-standard Amsterdam histology grading criteria denoting acute maternal versus infant-level inflammation. Relationships between histology, presence or absence of ROP, gestational age (GA), sex and birthweight (BW) were determined by univariate and multivariate analysis; infants were excluded if full clinical data were not available. In parallel, candidate ROP proteins were measured in cord blood specimens from a prospectively collected validation cohort of infants born prior to 31 weeks with (n=11) or without (n=12) acute placental inflammation using ELISA (HTRA1 and IGF1) or Luminex (VEGFA and TGFb-1). Protein values were correlated with histology outcomes using a one-tailed t-test.
Results :
182 infants met inclusion and exclusion criteria; 100 infants demonstrated presence of ROP. Univariate analysis demonstrated significantly positive correlations (p£0.1) between the presence of ROP, BW (p= 5.48e-09) and GA (p=6.56e-12); significant inverse correlations were identified between preeclampsia (p=0.03) and acute histologic placental inflammation (p=0.09). In multivariate analysis GA remained positively correlated with ROP (p=5.34e-09) and acute inflammation inversely correlated (p=0.02). BW and preeclampsia did not remain significant. Further analysis of placental inflammation by severity revealed significant inverse associations for both maternal-level (p=0.01) and infant-level (p=0.005) inflammation with the presence of ROP disease. Candidate proteins HTRA1 (p=0.003) and TGFb-1 (p=0.02) were significantly increased in cord blood from infants born in the setting of acute placental inflammation histology compared to non-inflammatory placental histology. Changes in VEGFA and IGF1 were not significantly associated with ROP development.
Conclusions :
Utilizing a systems biology-based approach, that included two independent cohorts, we demonstrate that preeclampsia, and moreover, placental inflammation is protective of ROP development. Data further suggests that protein changes in HTRA1 and TGFb-1 underlie the pathomechanisms between placental inflammation and ROP development.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.