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Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity

ABSTRACT: Retinopathy of prematurity (ROP), a blinding condition affecting preterm infants, accounts for up to 40% of all childhood blindness worldwide. ROP is an interruption of retinal vascular maturation, which is physiologically complete at full term and thus ongoing at the time of preterm birth. 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 examine the clinical associations between presence and severity of acute placental inflammation to ROP risk. Using logistic regression, we find a protective relationship between presence and severity of acute placental inflammation and preterm infant development of ROP. This is most significant for infants born in the absence of maternal preeclampsia. Further, we examine the underlying molecular mediators that may inform this protective paradigm. Adopting a candidate approach analyzing proteins with described ROP risk associations, we find that placental HTRA1 and FABP4 protein expression is significantly decreased within placental tissues characterized by acute inflammation. Additionally, HTRA1 and VEGFA demonstrate inverse longitudinal trends within the peripheral circulation for infants born in the presence compared to absence of acute placental inflammation. An agnostic approach, including whole transcriptome and differential methylation placental analysis, identifies novel mediators and pathways that may underly protection. Taken together, these data build on emerging literature showing disparate associations between acute placental inflammation and ROP development within preeclamptic or non-preeclamptic preterm infant populations and identifies novel placental mechanisms that may inform postnatal risk associations in preterm infants.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218039 | GEO | 2023/01/01

REPOSITORIES: GEO

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Project description:<p>N-3 polyunsaturated fatty acids (PUFAs) may prevent retinal vascular abnormalities observed in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). In the OmegaROP prospective cohort study, we showed that preterm infants who will develop ROP accumulate the n-6 PUFA arachidonic acid (ARA) at the expense of the n-3 PUFA docosahexaenoic acid (DHA) in erythrocytes with advancing gestational age (GA). As mice lacking plasmalogens ―that are specific phospholipids considered as reservoirs of n-6 and n-3 PUFAs― display a ROP-like phenotype, the aim of this study was to determine whether plasmalogens are responsible for the changes observed in subjects from the OmegaROP study. Accordingly, preterm infants aged less than 29 weeks GA were recruited at birth in the Neonatal Intensive Care Unit of University Hospital Dijon, France. Blood was sampled very early after birth to avoid any nutritional influence on its lipid composition. The lipid composition of erythrocytes and the structure of phospholipids including plasmalogens were determined by global lipidomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). LC-HRMS data confirmed our previous observations by showing a negative association between the erythrocyte content in phospholipid esterified to n-6 PUFAs and GA in infants without ROP (rho = -0.485, p = 0.013 and rho = -0.477, p = 0.015 for ethanolamine and choline total phospholipids, respectively). Phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) species with ARA, namely PtdCho16:0/20:4 (rho = -0.511, p < 0.01) and PtdEtn18:1/20:4 (rho = -0.479, p = 0.015), were the major contributors to the relationship observed. On the contrary, preterm infants developing ROP displayed negative association between PtdEtn species with n-3 PUFAs and GA (rho = -0.380, p = 0.034). They were also characterized by a positive association between GA and the ratio of ethanolamine plasmalogens (PlsEtn) with n-6 PUFA to PlsEtn with n-3 PUFAs (rho = 0.420, p = 0.029), as well as the ratio of PlsEtn with ARA to PlsEtn with DHA (rho = 0.843, p = 0.011). Altogether, these data confirm the potential accumulation of n-6 PUFAs with advancing GA in erythrocytes of infants developing ROP. These changes may be partly due to plasmalogens.</p>

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Placental Inflammation Significantly Correlates with Reduced Risk for Retinopathy of Prematurity

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