Allogenic Umbilical Cord versus Adult RBC Concentrates Transfusion for Anemia in Preterm Neonates: a Randomized Controlled Trial

Rationale:  Anemia requiring red blood cell (RBC) transfusion- a common problem in NICU- is primarily treated by repeated transfusion of adult-donor RBC (aPRBC). Its grave association with retinopathy of prematurity (ROP) in neonates- possibly due to early non-physiological replacement of HemoglobinF (HbF) with HbA, can be treated by replenishing HbF. Novelty Promising interim results of an Italian multi-site RCT (umBilical blOod to tRansfuse preterm Neonates - BORN trial) demonstrated feasibility and safety of allogenic umbilical cord red blood concentrates (uPRBC) transfusion in neonates. The novel use of cord blood, rendering waste to biologicals may be worthwhile for resource constrained settings, yet challenges of unchartered territory are expected. 

**Aim:**To demonstrate Umbilical Packed Red Blood Cells harvest is feasible and transfusion safe, and evaluate if its transfusion in early life can prevent mortality and severe ROP in very preterm neonates.

Hypothesis and research question: uPRBC transfusion compared to aPRBC in preterm neonates requiring transfusion therapy for anemia reduces the composite outcome of mortality and ROP requiring treatment significantly. In neonates born before 30w GA requiring transfusion for anemia (diagnosed by 32w PMA) (P), can umbilical cord (I) versus adult (C) donor derived RBC concentrates can significantly reduce the composite outcome of ROP requiring treatment* and mortality (O), at 40 weeks PMA or discharge, whichever is earlier (T)? (*Type I ROP (Type I ROP: Zone1 any stage with plus, zone1 stage3 with no plus, and zone2 stage2 or 3 with plus) and aggressive ROP)

Objectives:

Primary

To evaluate reduction in combined outcome of mortality and ROP requiring treatment among preterm neonates (<30w gestational age) being transfused uPRBC versus aPRBC for anemia.

Secondary

(i) To assess the incidence of severe (stage >3) ROP, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), hemodynamically significant PDA (hs PDA), intraventricular hemorrhage (IVH), sepsis (ii)To assess transfusion needs/efficacy and relevant biochemical parameters Hb/hematocrit change, transfusion frequency, interval between consecutive transfusions, median HbF level day 14 and 28 of transfusion

(iii) To determine the incidence of total adverse events during transfusions and those that could be attributed to previous transfusions; proportion of protocol deviations

Methods:  Along with ethical approvals, SOPs/checklists for rigorously standardizing processes will be undertaken. uPRBC processed from cord blood harvested from consenting pregnant females undergoing LSCS at term, will be stored appropriately by our blood-centre research team. Neonates (<30w GA having anemia <32w PMA) will be randomized to receive uPRBC (arm A) or aPRBC (arm B) dispensed in identical-looking bags. Transfusions will be closely monitored for adverse events (if any) and reported to DSMB. The subjects will be screened for ROP until discharge or 40w PMA. An intention-to-treat analysis will be done. 

Expected: outcome Demonstrating harvest is feasible and transfusion safe, uPRBC transfusion in early life maybe recommended for preventing mortality and severe ROP in very preterm neonates.