The association between red blood cell transfusion timing and the development of retinopathy of prematurity: Application of the two-phase theory

Purpose: Red blood cell (RBC) transfusions are believed to be associated with retinopathy of prematurity (ROP), but the underlying mechanism is not fully understood, partly due to the lack of information on RBC transfusion timing. The aim was to determine the association between the timing and amount of RBC transfusions and the development and severity of ROP. Methods: This retrospective dual-center cohort study included 1177 neonates born in 2004–2022 with a gestational age at birth ≤28 weeks. Primary outcomes were any stage ROP and severe ROP based on maximum staging. Phase I of ROP was defined as ≤32.0 weeks postmenstrual age and phase II as >32.0 weeks postmenstrual age. Logistic regression analyses were adjusted for gestational age at birth, small for gestational age, mechanical ventilation duration, postnatal corticosteroids, sepsis, and necrotizing enterocolitis. Results: Multivariate analysis showed independent associations with severe ROP for RBC transfusion (OR 5.1; 95% CI 1.8–14.3), number of RBC transfusions (OR 1.2; 95% CI 1.1–1.3), RBC transfusion in phase I (OR 2.5; 95% CI 1.2–5.3), number of RBC transfusions in phase I (OR 1.2; 95% CI 1.0–1.3), RBC transfusion in phase II (OR 4.1; 95% CI 2.7–6.3) and number of RBC transfusions in phase II (OR 1.9; 95% CI 1.5–2.4). Conclusion: Based on maximum ROP staging, RBC transfusions in phases I and II are both associated with a high risk of severe ROP. A randomized controlled trial is urgently needed to determine the potential effect of RBC transfusions in phase II on ROP progression.