Transfusion of Prematures Trial

Long-term outcomes of extremely low birth weight (ELBW) preterm infants, those weighing less
than or equal to 1000 g at birth, are poor and pose a major health care burden. Virtually all
of these infants are transfused, but at inconsistent hemoglobin (Hgb) thresholds.

The investigators propose in TOP to randomize infants less than or equal to 1000 g BW and <
29 weeks GA to receive red blood cell (RBC) transfusions according to one of two strategies
of Hgb thresholds, either a high Hgb (liberal transfusion) or a low Hgb (restrictive
transfusion) algorithm. It is currently unknown which transfusion strategy is superior. TOP
is powered to demonstrate which strategy reduces the primary outcome of death or
neurodisability in survivors at 22-26 months.

A secondary study entitled "Effect of Blood Transfusion Practices on Cerebral and Somatic
Oximetry", also known as the NIRS study, will determine differences in cerebral oxygenation
and fractional tissue oxygen extraction with NIRS between high and low hemoglobin threshold
groups during red blood cell transfusions. The investigators also propose to determine
whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone
and whether abnormal mesenteric NIRS measures are associated with the development of NEC
within the 48 hours following a transfusion.

Extended follow-up: Subjects will be seen for a follow-up visit at 5-6 years corrected age to
assess neurological and functional outcomes at early school age based on neonatal transfusion
threshold.

Inclusion Criteria:

- Birth weight less than 1000 grams.

- Gestational age at least 22 weeks but less than 29 completed weeks

- Admitted to the NICU within 48 hours of life

Exclusion Criteria:

- Considered nonviable by the attending neonatologist

- Cyanotic congenital heart disease

- Parents opposed to the transfusion of blood

- Parents with hemoglobinopathy or congenital anemia

- In-utero fetal transfusion

- Twin-to-twin transfusion syndrome

- Isoimmune hemolytic disease

- Lack of parental consent

- Severe acute hemorrhage, acute shock, sepsis with coagulopathy, or need for
perioperative transfusion.

- Prior blood transfusion on clinical grounds beyond the first 6 hours of life

- High probability that the family is socially disorganized to the point of being unable
to attend follow-up at 22-26 months.