The newborn period marks a time when red blood cell (RBC) indices change significantly. Anemia can occur at various times in the neonatal period, from the perinatal and immediate postnatal period through the first months of life. Hematocrits 2 or more standard deviations below the normal range for gestation are seen frequently and should be evaluated. Conversely, true anemia, the inability to adequately deliver oxygen to tissues, is less common. Anemia can be classified into the following 3 major processes: hemolysis, hemorrhage, or hypoproliferative disease. Anemia can also result from overlapping processes. For example, sepsis can result in hemolysis, disseminated intravascular coagulation (DIC), and subsequent hemorrhage. This chapter reviews fetal and neonatal erythropoiesis, discusses the etiology and diagnosis of anemia in the neonatal period, and offers management options for anemic term and preterm infants.
The growth factors stimulating fetal erythropoiesis during gestation are produced solely by the fetus. Erythropoietin, or Epo, is the primary growth factor responsible for erythropoiesis after birth and appears to be the principal growth factor for fetal erythropoiesis as well. Primary production of Epo occurs in the liver during fetal development. The kidney becomes the primary source of Epo following delivery; however, the etiology for the liver-to-kidney switch continues to be studied. Anephric fetuses have normal serum Epo concentrations and normal hematocrits, proving that renal Epo production is not required for erythropoiesis during fetal development. Methylation patterns in the promoter and enhancer regions of the Epo gene isolated from fetal liver and kidney suggest increased methylation in the kidney as a possible explanation for decreased Epo gene expression during fetal development.
During gestation, the site of red cell production transitions from yolk sac to liver to marrow. Primitive erythroblasts are produced in the fetal yolk sac during the first 3–4 weeks of gestation. By 6 to 8 weeks’ gestation, definitive erythropoiesis is established in the fetal liver. Although erythrocytes are noted in the fetal marrow as early as 8–9 weeks’ gestation, the liver remains the primary site of erythropoiesis until well into the second trimester. By the third trimester, erythropoiesis occurs primarily in the fetal marrow, although production can continue in extramedullary sites in the face of increased need, during times of hemolysis, or in fetal infection caused by a variety of bacteria or viruses.
Variations in hematologic indices for preterm and term infants reflect the dynamic nature of the erythron in late fetal development. The production of hemoglobin transitions from embryonic (Gower 1 [ζ2ε2], Gower 2 [α2ε2], and Portland [ζ2γ2]) to fetal hemoglobin (α2γ2) and finally to adult hemoglobin (α2β2), as shown in Figure 31-1.
Changes in hemoglobin production from conception through 40 weeks postnatal age.