Preventing Anemia in the NICU

The average life span of fetal hemoglobin, which continue to be produced during early infancy, is 50 to 90 days compared to the 120-day life span of adult hemoglobin.⁷ Thus, the red blood cell turnover is more rapid. If the bone marrow is not increasing the production of red blood cells, there is a net loss of red blood cells.

Further losses may occur through phlebotomy. The primary cause of anemia among preterm infants during the first weeks of life is blood loss attributable to laboratory testing. Use of instruments for a given blood test that require large blood volumes and collection in blood containers without fill-lines exacerbate the problem.

An infant who was quite functional with AOP may become symptomatic after repeated blood draws. Increased episodes of apnea, bradycardia, poor feeding, increased oxygen requirements, and even respiratory failure necessitating intubation and ventilation may result.

As neonatal intensive care practices have advanced, lighter weight infants and more critically ill infants with greater need for blood draws are being cared for in the NICU. In a study of 60 VLBW infants during the first 28 days after birth, researchers showed infants who required no ventilator support had a lower blood volume loss of 24 mL/kg when compared to infants who required minor ventilator support (60 mL/kg blood loss), and infants who required ventilator support for respiratory distress syndrome (67 mL/kg blood loss).⁹ A high correlation (rs = +0.91) was found between the blood volumes sampled and transfused.

Of note, in the 24 hours before and after a blood transfusion, the infants who required some form of ventilator support showed poorer weight gain and an increased incidence of pallor and distended abdomen, the most frequent symptoms of anemia.

No Set Guidelines
The Premature Infant in Need of Transfusion (PINT) study demonstrated that transfusing infants to maintain a high hemoglobin level (8.5-13.5 g/dL) confers no benefit in terms of mortality, severe morbidity, or apnea intervention compared with infants transfused to maintain a low hemoglobin level (7.5-11.5 g/dL).¹⁰

Similarly, an evaluation of transfusion guidelines in VLBW infants found when increasingly restrictive transfusion guidelines were implemented, the transfusion number decreased by 71 percent, and the donor exposure decreased by 80 percent in these infants without adverse clinical effects.¹¹

In comparison, a study showed significantly fewer brain injuries and less frequent apnea in infants whose transfusion criteria was not restricted and whose hemoglobin level was higher.¹² Some physicians remain concerned that if we restrict the criteria for blood transfusions, we also may decrease oxygen delivery to vulnerable organs such as the brain.

While no set guidelines for transfusion in infants with AOP have been prescribed, audit criteria and indications for transfusions suggested by various studies lend themselves to following transfusion guidelines that restrict blood transfusions to specific infants who have significant anemia and who are symptomatic.^11-13 This has led most NICUs to adopt criteria whereby hemoglobin or hematocrit below a certain level alone will not trigger a blood transfusion automatically.^11-13

Recombinant Erythropoietin
What can be done to prevent the predictable decline in EPO production and the preterm infant's relative insensitivity?

Some have advocated and shown recombinant EPO can mitigate the exaggerated anemia.^2-5,14 Why not give all preterm infants recombinant human erythropoietin replacement (rhEPO) then? Trials evaluating the effect of rhEPO treatment in populations of the most immature neonates have had mixed results.

Consistently, it has been shown that VLBW infants are capable of responding to rhEPO with a reticulocytosis and that the drug appears to be safe; however, its beneficial effects are not seen for at least two weeks.^4,14,15 rhEPO with iron does not adversely affect growth or developmental outcomes, but the effect on the number of transfusions a premature infant receives ranges from nonexistent to small.

There has been little agreement regarding timing, dosing regimens, administration route, or therapy duration. The cost-benefit ratio is another consideration. When the family has religious objections to transfusions, the use of rhEPO is advisable.