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Anemia of prematurity

Joseph A Garcia-Prats, MD
Section Editors
Steven A Abrams, MD
Donald H Mahoney, Jr, MD
Deputy Editor
Melanie S Kim, MD


Erythropoiesis decreases after birth as a result of increased tissue oxygenation due to the onset of breathing and closure of the ductus arteriosus, and a reduced production of erythropoietin (EPO) [1]. In term infants, the hemoglobin level typically reaches an average nadir of 11 g/dL at approximately 8 to 12 weeks after birth.

In preterm infants who are already born with a lower hematocrit, this decline, referred to as anemia of prematurity (AOP), occurs earlier and is more pronounced in its severity than the anemia seen in term infants. The AOP will be reviewed here.


The primary cause of anemia of prematurity (AOP) is the impaired ability to increase serum erythropoietin (EPO) appropriately in the setting of anemia and decreased tissue availability of oxygen [2,3]. Circulating and bone marrow red cell progenitors respond to EPO, if present, indicating that the impaired erythropoiesis is due to lack of EPO, not a failure to respond to the hormone [4-6]. Other hematopoietic growth factors (eg, granulocyte-macrophage colony-stimulating factor) are not affected.

Impaired erythropoietin production — EPO is produced by the fetal liver and the cortical interstitial cells of the kidney in response to hypoxia. Its production is regulated by the transcription factor hypoxia inducible factor-1 (HIF-1). Its primary function is to regulate erythrocyte production. EPO does not cross the placenta in humans, and fetal production increases with gestational age [7-10].

Production of EPO in adults depends on the oxygen saturation of hemoglobin and tissue oxygen delivery, and is inversely proportional to central venous oxygenation. Although EPO levels in preterm infants with AOP increase slightly with hypoxia, they are lower than those seen in older children and adults with the same level of anemia [2,11]. (See "Regulation of erythropoiesis".)

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Literature review current through: Nov 2017. | This topic last updated: Aug 17, 2017.
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