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Nucleated Red Blood Cells

Circulating erythrocyte precursors (nucleated red blood cells or normoblasts) are frequently found in the peripheral blood of newborns. In the normal term neonate, nucleated red blood cells (nRBCs) are rapidly cleared from the bloodstream after birth. However, in the preterm neonate, low numbers of nRBCs may persist throughout the first week of life. Absolute numbers of nRBCs may be reported in relation to the number of white blood cells (nRBCs/100 white blood cells) or expressed as an absolute number per unit volume (nRBCs/mm3). The upper limit of the normal range for nRBCs in the term infant is 1000 nRBCs/mm3, with preterm newborns typically having greater numbers of nRBCs in the immediate postnatal period compared to term neonates.

Elevated nRBC numbers or their persistence in the peripheral circulation may result from either increased erythropoiesis and/or stress-related release of normoblasts from the bone marrow. Increased erythropoiesis can occur as a result of pathological events, such as fetal hypoxia secondary to placental insufficiency and/or preeclampsia, or can be secondary to blood loss, including hemolysis. In infants of diabetic mothers, elevated nRBC concentrations are also observed, driven by an increase in erythropoiesis secondary to elevated erythropoietin concentrations and a direct hematopoietic action of hyperinsulinemia. Maternal smoking during pregnancy can also increase nRBCs.

Hypoxia does not need to be chronic to result in increased nRBCs in the immediate newborn period. Nucleated RBCs have been shown to be raised in infants following acute perinatal asphyxia. This is thought to result from an increase in interleukin-6 immediately following the hypoxic insult. A prolonged elevation in nRBCs then continues, secondary to erythropoietin stimulation. Previously, nRBCs were thought to represent a useful biomarker for the degree of perinatal asphyxia. While they may discriminate mild from moderate/severe encephalopathy in normothermic infants, this association is lost in infants receiving therapeutic hypothermia.


Hemoglobin, located in the red cell, is a heme-containing metalloprotein comprising 4 globin chains. These chains undergo conformational change in the context of oxygen binding, with each gram capable of carrying 1.34 mL of oxygen. The globin chains change from fetal life to infancy with adult globin chain predominating by 6 months of age. The mean hemoglobin concentration in the term newborn ranges from 14 to 20 g per 100 mL. The thalassemia syndromes (α and β) occur from abnormalities in globin chain synthesis (see Chapter 430).

Causes of Anemia

Erythropoietin (EPO) is a glycoprotein produced by the kidney in the setting of hypoxia. Stimulation of EPO release in the context of relative hypoxia in utero, results in a surge of RBC production leading to high red cell population at birth. After birth, EPO is subsequently down-regulated as a result of the transition to the relatively oxygen-rich extra-uterine environment thus leading to a fall in hemoglobin ...

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