Transfusion-Free Survival Predicts Severe Retinopathy in Preterm Neonates

Abstract

Repeated red blood cell (RBC) transfusions are thought to increase the risk for retinopathy of prematurity (ROP), likely due to a critical fetal hemoglobin (HbF) reduction. In this study, we investigated if the postmenstrual age (PMA) of neonates at transfusion influences the risk for ROP. We estimated the cumulative transfusion-free survival (TFS) in a series of 100 preterm neonates receiving one or more RBC units. TFS was calculated by censoring patients at first transfusion and expressing the time between birth and transfusion as either PMA or postnatal day. Then, we investigated if TFS predicted the occurrence of severe ROP, defined as ROP stage 3 or higher. We found that neonates with severe ROP displayed a significantly shorter TFS expressed according to their PMA (p = 0.001), with similar TFS according to postnatal days. At receiver operating characteristic (ROC) curve analysis, receiving an RBC unit before week 28 of PMA predicted severe ROP with a sensitivity of 64% and a specificity of 78%. In addition, receiving a second RBC unit before the PMA of 29 weeks predicted severe ROP with a sensitivity of 75% and a specificity of 69%. At multivariate analysis, PMA at the second transfusion was even more informative than at first transfusion and outperformed all other variables in predicting severe ROP, with an odds ratio of 4.554 (95% CI 1.332-15.573, p = 0.016). Since HbF decrease is greater after multiple RBC transfusions, it is conceivable that neonates receiving more than one unit before the PMA of 29 weeks may be exposed to a greater disturbance of retinal vascularization. Any strategy aimed at preventing the critical HbF decrease at this low age might potentially reduce the risk for severe ROP.

Keywords: RBC transfusion; fetal hemoglobin; postmenstrual age; preterm birth; retinopathy.

Figure 1

Retinal vessels development occurs through vasculogenesis and angiogenesis in a well-specified period of gestation, starting before week 15 and concluding around week 31. At the bottom are displayed the cases of three neonates, all receiving two RBC units at postnatal days 9 and 14 (red arrows). According to postmenstrual age, at the beginning of week 28, patient 1 had received no transfusion, patient 2 had received one single transfusion, and patient 3 was given two transfusions. RBC, red blood cell.

Figure 2

Flow diagram on the inclusion/exclusion criteria and final cohort of investigated patients. PMA, postmenstrual age; ROP, retinopathy of prematurity.

Figure 3

Cumulative transfusion-free survival in the initial cohort of 100 transfused patients. The survival was estimated censoring patients at first RBC transfusion event, expressed according to postnatal day (A) or postmenstrual weeks (B). The distribution of RBC unit needs is also displayed (inset in A). RBC, red blood cell.

Figure 4

Cumulative transfusion-free survival in the initial cohort of 100 transfused patients. Patients were variably grouped according to different clinical outcomes: documented infections, multiple documented infections, suspected infectious episodes not followed by pathogen identification, intraventricular hemorrhage (IVH), necrotizing enterocolitis requiring surgery, and death.

Figure 5

Cumulative transfusion-free survival in a cohort of 72 transfused neonates, grouped according to the occurrence of stage 3 or higher retinopathy of prematurity (ROP). (A) Transfusion-free survival estimated according to postnatal day at first RBC transfusion does not significantly differ between patients with and without severe ROP. (B) Transfusion-free survival estimated according to postmenstrual age at first transfusion is significantly lower in neonates developing severe ROP. (C) The difference between groups is even greater if survival to the second RBC transfusion event is considered. RBC, red blood cell.