Aggressive Posterior Retinopathy of Prematurity Is Associated with Multiple Infectious Episodes and Thrombocytopenia

Abstract

Background: The most severe form of rapidly progressing retinopathy of prematurity (ROP) is termed aggressive posterior ROP (APROP). APROP frequently causes severe visual impairment in affected preterm infants despite timely and appropriate laser treatment. Objectives: We investigated the postnatal characteristics associated with APROP development in a national Swedish cohort. Methods: This retrospective, 1:1 matched case-control study included all infants that developed APROP in zone 1 (n = 9) between 2008 and 2012. Control infants, matched for gestational age and birth weight, developed ROP no worse than stage 2 (n = 9). We retrieved data from medical records on infant birth characteristics, postnatal morbidities, and blood analyses from birth to the first ROP treatment. Infectious episodes included sepsis, C-reactive protein ≥10 mg/l, and other clinical signs of infection that required antibiotic treatment. A platelet count <100 × 10⁹/l was considered to be thrombocytopenia. Results: All APROP cases postnatally developed at least two infectious episodes, one in the first month and one around the time of ROP diagnosis. All APROP cases exhibited thrombocytopenia in the first month, and 6/9 exhibited thrombocytopenia around the time of ROP diagnosis. Compared to the controls, APROP cases more frequently developed necrotizing enterocolitis (8/9 vs. 1/9; p < 0.01) and sepsis (9/9 vs. 3/9; p < 0.01), and they had significantly lower median platelet counts (90 × 10⁹/l, range 4-459, vs. 158 × 10⁹/l, range 20-500; p < 0.001). Conclusion: Multiple infectious episodes and thrombocytopenia, particularly around the time of ROP diagnosis, were associated with APROP development.

Chorioamnionitis as a risk factor for retinopathy of prematurity: an updated systematic review and meta-analysis

“…That the fetal inflammatory response induced by CA might specifically influence the development of the fetal retina is a biologically plausible hypothesis. It has been suggested that multiple hits of antenatal and postnatal infection/inflammation are involved in ROP etiology and progression [15,27,90,91]. Retinal vascular development occurs while the fetus is in the uterus in a relatively hypoxic environment.…”

“…Of note, our meta-analysis could not demonstrate that CA was a significant risk factor for ROP stage 1-2 (Fig 4). Recent clinical data suggest that infection/inflammation mechanisms are mainly related to the more advanced stages of ROP, particularly the so-termed aggressive posterior ROP (APROP) [27,90].…”

“…However, part of the effects of CA on the pathogenesis of ROP may be mediated by the role of CA as an etiological factor for very preterm birth. that multiple hits of antenatal and postnatal infection/inflammation are involved in ROP etiology and progression [15,27].…”

“…However, part of the effects of CA on the pathogenesis of ROP may be mediated by the role of CA as an etiological factor for very preterm birth. that multiple hits of antenatal and postnatal infection/inflammation are involved in ROP etiology and progression [15,27].The role of CA as a potential pathogenic factor for ROP has already been the subject of a systematic review and meta-analysis [28]. Mitra et al [28] included 27 studies (10,590 preterm infants) in their review.…”

The association of platelet counts with development and treatment for retinopathy of prematurity – is thrombocytopenia a risk factor?

“…Similarly, we found that the risk of ROP development increased with the number of days with thrombocytopenia, but with borderline significance. It is possible that the decrease in platelet count may be a response to sepsis, which in turn, according to Lundgren et al and Guida et al, may be associated with APROP [8,9]. To date, anemia and blood transfusions were considered the hematologic risk factors for ROP development [10].…”