Perinatal infection, inflammation, and retinopathy of prematurity

Abstract

The major known risk factors for retinopathy of prematurity (ROP) are extremely low gestational age, exposure to high levels of oxygen early after birth (phase I) and relatively lower oxygen levels later (phase II). In this review, we summarize recent data suggesting that exposure to perinatal infection/inflammation is associated with an increased risk for ROP. Part of this effect might be due to direct exposure of the developing retina to circulating products of infection and/or inflammation. Another potential mechanism that deserves exploration is that inflammation and/or oxidative stress can modify the known increased risk of oxygen-associated ROP. Taken together, accumulating evidence suggests that prenatal, perinatal, and postnatal systemic inflammation contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent insults, setting the stage for what are now called phase I and phase II of ROP pathogenesis. Strategies targeting inflammatory responses might help reduce the risk for ROP in extremely low gestational age newborns.

Figure 1

Proposed multi-phase model of retinopathy of prematurity (ROP) pathogenesis. In the pre-phase, prenatal pro-inflammatory events such as intrauterine infection and pre-eclampsia contribute to fetal inflammation and sensitization to subsequent postnatal insults. In phase I, preterm infants’ developing retinas are exposed to hyperoxia relative to in-utero oxygen levels, resulting in retinal vessel growth attenuation. Prenatal exposure to inflammation seems to exacerbate effects of postnatal factors. In phase II, retinal growth leaves part of the retina hypoxic, thereby stimulating intense neovascularization around 32 weeks of postmenstrual age (PMA), which in turn leads to high grade ROP.