Neonatal anemia

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Summary

Neonatal anemia and the need for red blood cell (RBC) transfusions are very common in neonatal intensive care units. Neonatal anemia can be due to blood loss, decreased RBC production, or increased destruction of erythrocytes. Physiologic anemia of the newborn and anemia of prematurity are the two most common causes of anemia in neonates. Phlebotomy losses result in much of the anemia seen in extremely low birthweight infants (ELBW). Accepting a lower threshold level for transfusion in ELBW infants can prevent these infants being exposed to multiple donors.

Introduction

Neonatal anemia is defined by a hemoglobin or hematocrit concentration of greater than 2 standard deviations below the mean for postnatal age.1 The etiology of neonatal anemia is commonly subdivided into three major categories: blood loss, decreased production, and increased destruction of erythrocytes (Box 1). Hematopoiesis in the fetus and neonate is in a constant state of flux and evolution as the newborn adapts to a new milieu.

Fetal erythropoiesis occurs sequentially during embryonic development in three different sites: yolk sac, liver, and bone marrow.2 Yolk-sac formation of red blood cells (RBCs) is maximal between 2 and 10 weeks of gestation. Myeloid (bone marrow) production of RBCs begins at around week 18 and, by the 30th week of fetal life, bone marrow is the major erythropoietic organ. At birth, almost all RBCs are produced in the bone marrow, although a low level of hepatic erythropoiesis persists through the first few days of life. RBC production in extrauterine life is controlled in part by erythropoietin (EPO) produced by kidney.

Hemoglobin, hematocrit, and RBC count increase throughout fetal life. Extremely large RBCs with an increased content of hemoglobin (Hb) are produced early in fetal life. The size and Hb content of these cells decrease throughout gestation, but the mean corpuscular hemoglobin concentration (MCHC) does not change significantly. During the neonatal period, the newborn leaves the relatively hypoxic in-utero environment and emerges into a different physiologic setting.

Section snippets

Physiologic anemia of infancy

When infants take their first breath, considerably more oxygen is available for binding to Hb, and Hb oxygen saturation increases from approximately 50% to 95% or more. The normal developmental switch from fetal to adult Hb synthesis actively replaces high-oxygen-affinity fetal Hb with low-oxygen-affinity adult hemoglobin, which can deliver a greater fraction of Hb-bound oxygen to the tissues. Therefore, immediately after birth the increase in blood oxygen content and tissue oxygen delivery

Anemia of prematurity

The physiologic anemia seen in preterm infants is more profound and occurs earlier than anemia of infancy. Various causes contribute to this condition. An important component in the first few weeks of life is blood loss due to sampling for the many laboratory tests that premature infants undergo. The erythropoietic response is also suboptimal, a significant problem because demands on erythropoiesis are heightened by the short survival of the RBCs from premature infants (approximately 40–60 days

Blood loss

Blood loss in neonates can occur before, during, or after delivery, and can account for 5–10% of all cases of severe neonatal anemia.16 Anemia frequently follows fetal blood loss, bleeding from obstetric complications, and internal hemorrhages associated with birth trauma.

Iatrogenic anemia due to repeated removal of blood for laboratory testing is common in premature infants. Most affected infants are asymptomatic but when losses approach 20% of total blood volume, signs and symptoms of

Diagnosis

Bleeding in the newborn is usually obvious because external bleeding can be perceived. It becomes difficult if the bleeding is not obvious. Rapidly developing anemia with hyperbilirubinemia and reticulocytosis, and absence of specific signs of the different types of hemolytic anemia, should lead to the diagnosis of internal bleeding. Thus the presence of signs of regeneration, without evidence of blood destruction, should lead to the suspicion of bleeding inside the body. A Kleihaur Betke's

Issues in transfusion

The goal of transfusion in infants with anemia of prematurity is to ‘restore or maintain oxygen delivery without increasing oxygen consumption’.38 Transfusion practices vary markedly across units and there is a lack of evidence-based studies to guide practice.39 None of the clinical signs has been consistently useful – either alone or as a group – in determining when to transfuse an infant with low hemoglobin of (physiologic) anemia of prematurity and iatrogenic losses. The decision to

Donor issues

A concern for infants who might need multiple transfusions is exposure to multiple donors. The use of multiple donors increases the risk of infection and transfusion reactions. Donor exposure can be reduced for infants who need small-volume transfusions (<15–20 ml/kg) by using stored packed red blood cells (PRBCs) from a single unit (Table 1). This unit is divided into multiple aliquots that are reserved for a specific infant. This procedure has reduced donor exposure to one or two donors for

Prevention of late nutritional anemia

Both term and preterm infants should be discharged from the hospital on supplemental iron, either as iron-fortified formulas or as an oral supplement of 2–3 mg/kg per day elemental iron for breastfed infants. Enteral iron supplementation is feasible and probably safe in infants with birth weight <1301 g.44 Iron supplementation can reduce the incidence of iron deficiency and the number of late blood transfusions.

Iron deficiency can occur in very low birthweight infants despite early

A diagnostic approach to the newborn with anemia

The establishment of an accurate diagnosis is essential to directing the appropriate therapeutic interventions. Thorough history taking and physical examination are the primary steps in identifying the condition and establishing an etiology, but further investigations in the form of laboratory testing are often required to differentiate the many possible causes.

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