Anemia of Prematurity

Background Anemia of prematurity (AOP) is an exaggerated, pathologic response of the preterm infant. AOP is a normocytic, normochromic anemia characterized by low serum EPO levels. Nutritional deficiencies of iron, vitamin E, vitamin B-12, and folate may exaggerate the degree of anemia, as may blood loss and/or a reduced red cell life span. The risk of anemia of prematurity (AOP) is inversely related to gestational maturity and birthweight. As many as half of infants of less than 32 weeks gestation develop AOP.

Etiology Three basic mechanisms for the development of anemia of prematurity (AOP) include: inadequate RBC production shortened RBC life span blood loss.

Presentation Many clinical findings have been attributed to anemia of prematurity (AOP), but they are neither specific nor diagnostic. These symptoms may include the following: Poor weight gain despite adequate caloric intake Cardiorespiratory symptoms such as tachycardia, tachypnea, and flow murmurs Decreased activity, lethargy, and difficulty with oral feeding Pallor Increase in apneic and bradycardic episodes, and worsened periodic breathing Metabolic acidemia - Increased lactic acid secondary to increased cellular anaerobic metabolism in relatively hypoxic tissues

Treatment Medical treatment options: Blood transfusion(s) Recombinant erythropoietin (EPO) Observation.

Observation Observation may be the best course of action for infants who are asymptomatic, not acutely ill, and are receiving adequate nutrition. Adequate amounts of vitamin E, vitamin B-12, folate, and iron are important to blunt the expected decline in hemoglobin levels in the premature infant. Periodic measurements of the hematocrit level in infants with AOP are necessary.

"Blood transfusion is like marriage; it should not be entered into lightly, unadvisedly or wantonly, or more often than is absolutely necessary." R.W. Beal (1976)

PRBC Transfusions The frequency of blood transfusion varies with gestational age, degree of illness, and, interestingly, the hospital evaluated. There is considerable disagreement about the indication, timing, and efficacy of PRBC transfusion. The decision to give a transfusion should not be made lightly, because significant infectious (HIV: 1: 2-3 million, Hep C: 1: 1.6 million, Hep B:1: 200,000 – 300,000), hematologic, immunologic, and metabolic complications are possible. Late-onset necrotizing enterocolitis has been reported in stable-growing premature infants electively transfused for AOP. Transfusions also transiently decrease erythropoiesis and EPO levels. There is also agreement that the number of transfusions, as well as the number of donor exposures, should be reduced as much as possible.

Non-transfusion Approaches Decrease lab draws Enteral iron Delayed cord clamping Restrictive transfusion policies

New Transfusion Guidelines March 2010 Transfusion Threshold Clinical Situation Hgb < 10g/dL Critically ill neonate, ventilated or significant pressor support Hgb < 8g/dL Infant on stable respiratory support (CPAP/stable vent, HFHNC for CPAP effect, or NC Hgb < 7g/dL Infant requiring no support

EPOgen Multiple investigations have established that premature infants respond to exogenously administered recombinant human EPO and supplemental iron with a brisk reticulocytosis. Although EPO cannot prevent early transfusions, modest decreases in the frequency of late PRBC transfusions have been documented. Additional iron supplementation is necessary during exogenous EPO treatment.

EPOgen (cont) Studies and a Cochrane Neonatal Systemic review suggest an association between exogenous EPO administration and retinopathy of prematurity. Yasmeen et al studied 60 preterm low birth weight infants and concluded that short-term recombinant human erythropoietin with iron and folic acid was effective in preventing anemia of prematurity. EPO with iron does not adversely affect growth or developmental outcomes, but the impact on the number of transfusions a premature infant receives ranges from nonexistent to small. At this time, no agreement regarding the safety, timing, dosing, route, or duration of therapy has been established. In short, the cost-benefit ratio for EPO has yet to be clearly established, and this medication is not universally accepted as a standard therapy for an infant with AOP.