The investigators seek to determine whether providing inhaled nitric oxide (iNO; a vasodilator) will improve the delivery of oxygen to the brain, kidney and intestines of preterm neonates during and after the subject receives a packed red blood cell transfusion (PRBC) for anemia vs. baseline period. The investigators will observe the effect of inhaled nitric oxide vs. placebo at these body sites to determine whether iNO will alter the fractional tissue oxygen extraction. Treatment and control groups will be compared to each other at equivalent epochs as will individual patients before, during and after the PRBC transfusion.

Selection criteria: 1) Neonates 24 0/7 to 27 6/7 weeks gestational age (GA) 2) More than 2 weeks postnatal age. 3) Anemia with Hct less than 28 % 4) >50 % total daily fluids is enteral 5) History of at least 1 prior PRBC transfusion ELGANs admitted to the neonatal intensive care unit (NICU) will be screened for the study. If patients meet the selection criteria, parents will be approached to obtain informed consent. Then the patient will be randomized to either iNO or placebo group before treatment. The treating physician will make the decision regarding timing of the PRBC transfusion to treat anemia for the subject.

During the period of observation, near infrared spectroscopy (NIRS) monitoring will be performed on all enrolled subjects during which a non-invasive probe will be attached to the skin at 3 sites simultaneously- on abdomen below umbilicus, flank/back, and forehead for calculation of fractional tissue oxygen extraction ( FTOE) in conjunction with concurrent pulse oximetry recordings.

Conventional vital signs, blood gas, lactate, haptoglobin and cytokines will be measured before and after the PRBC transfusion

Inclusion Criteria:

• Neonates 24 0/7 to 27 6/7 weeks gestational age
• More than 2 weeks postnatal age.
• Anemia with hematocrit (Hct) less than 28 %
• More than 50 % total daily fluids is enteral
• History of at least 1 prior PRBC transfusion (preferably same donor)

Exclusion Criteria:

• Prior history of necrotizing enterocolitis (NEC) to avoid a confounder
• Clinically significant patent ductus arteriosus (PDA) requiring treatment (Rx) within 24h
• Hypotensive for age or active bleeding
• < 50% of total fluids are enteral (breast milk or formula)
• Major congenital or surgical malformations
• Known chromosomal anomalies detected by antepartum testing or direct physical examination with subsequent postnatal laboratory confirmation
• Absence of parental or treating physician consent
• A concurrent randomized clinical trial (RCT) with another randomized drug
• Death expected < 48h
• Another major concern by the treating physician that either mandates or prohibits study treatment such as known adverse reaction to prior transfusion (Tx)

After publication of the primary manuscript.

After publication of the primary manuscript

Data available if there is a well thought-out plan from a credible investigator who is exeprineced in neonatology, transfusion medicine or control of the microcirculation via nitric oxide.

iNO vs nitrogen will be administered from tanks labeled with a code number that is known by the manufacturer and a campus safety officer but masked to investigators and to bedside personnel.