Transfusion-related Inflammatory Cytokine and Neutrophil Extracellular Trap Quantification in Neonates

Despite many advances in neonatal care, necrotizing enterocolitis (NEC) remains a leading
cause of morbidity and mortality among premature infants. NEC is the most common
life-threatening gastrointestinal emergency encountered in the neonatal intensive care unit,
affecting between 3.8% and 13% of very low birthweight (VLBW) infants (1-3). More recently
interest has intensified regarding the possible association between "elective" red blood
cell (RBC) transfusions in premature infants and the subsequent development of NEC (4-9).
On a physiological basis, a few explanations for transfusion-associated NEC have been
proposed: 1) the physiological impact of anemia that can initiate a cascade of events
leading to ischemic-hypoxemic mucosal gut injury predisposing to NEC [10]; and 2) increased
splanchnic blood flow following RBC transfusion leading to reperfusion injury of gut mucosa.

Aim 1. This study will quantify inflammatory cytokine profiles in anemic infants cared for
in the NICU prior to and after transfusion with packed red blood cells (PRBC), as dictated
by current clinical guidelines for treatment of anemia, and prospectively assess for
clinical signs and symptoms of NEC following each transfusion event.

Aim 2. Polymorphonuclear leukocytes (PMNs) isolated from the pre- and post-transfusion
blood samples will be assessed in vitro for neutrophil extracellular traps (NET) formation.

Aim 3. A) To determine whether significant anemia preceding a RBC transfusion is associated
with impaired intestinal oxygenation, and whether a RBC transfusion temporarily increases
splanchnic oxygenation. We postulate that the CSOR will be low (<0.75) at baseline
measurement in infants with hemodynamically significant anemia, and that RBC transfusion
will temporarily increase intestinal perfusion in that particular group of babies.

B) To determine whether alterations in mesenteric regional oxygenation saturation(rSO2) can
predict the development of NEC in VLBW infants. We hypothesize that overall
cerebro-splanchnic oxygenation ratio (CSOR) values will be significantly lower among very
low birth weight (VLBW) infants that develop NEC, when compared to CSOR values obtained in
infants that do not develop NEC following RBC transfusion.