Review the definition, risk factors, pathogenesis, clinical symptoms, diagnosis, outcomes, and clinical management of neonatal anemia.
Neonatal anemia, a common condition in the neonatal intensive care unit (NICU) is defined as a hemoglobin (Hb) or hematocrit (Hct) concentration greater than two standard deviations below the mean for postnatal age and can be classified based on etiology into three categories: blood loss, inadequate red blood cell (RBC) production, and increased RBC destruction.
Blood loss due to significant bleeding can occur prior to, during, or after delivery. Fetomaternal hemorrhage is often small volume and clinically insignificant, but in severe cases can be catastrophic. External bleeding after delivery is usually obvious, but internal bleeding can be much more difficult to detect.
Inadequate RBC production is particularly common in the preterm neonate.
Erythropoiesis is in a constant state of evolution during the fetal and perinatal periods. Hb, Hct, and RBC counts vary throughout fetal life, and RBC indices and morphology at birth are different from pediatric or adult reference ranges. Compared to adult Hb, fetal Hb in the hypoxic fetal environment has a higher affinity for oxygen. As a newborn starts to breathe in the relatively high-oxygen environment at birth, Hb oxygen saturation increases rapidly. This induces a physiologic transition from fetal to adult Hb—which has a lower oxygen affinity—to facilitate increased delivery of Hb-bound oxygen to the tissues.
RBC production is stimulated by erythropoietin (EPO), which is downregulated by increased tissue oxygen delivery after birth. Erythropoiesis remains suppressed until tissue oxygen needs are greater than oxygen delivery. For term neonates, this nadir (Hb of 9.5–11 g/dL or Hct of 28.5–33%) is reached around 6–12 weeks of life, at which point EPO production increases and RBC production resumes. This is known as physiologic anemia of infancy.
For anemia of prematurity (AOP) in the preterm infant, this nadir is even more profound (typically ∼Hb 8 g/dL or Hct 24% for infants 1000–1500 g and ∼Hb 7 g/dL or Hct 21% for infants less than 100 g) and occurs earlier (4–8 weeks). One reason is the shorter lifespan—40–60 days—of RBCs in the premature neonate compared to 120 days in adults. In addition, EPO production in the preterm infant occurs in the liver, rather than the kidney, which is less responsive to anemia and hypoxia, leading to a blunted erythropoietic response. Finally, inadequate iron stores in the preterm infant further impair the ability of a preterm neonate to recover from anemia. Phlebotomy is a major iatrogenic contributor to AOP, and studies have demonstrated that phlebotomy volumes in the first 28 days of life represent up to 45% of total blood volume for preterm infants.
Increased RBC destruction (decreased RBC survival) is another important cause of neonatal ...