Anemia
Asimenia I. Angelidou
Helen A. Christou
KEY POINTS
A postnatal fall in hemoglobin is physiologically expected in all infants due to suppression of erythropoietin production in the relatively hyperoxic extrauterine environment reaching nadir between 8 and 12 weeks of age. The degree of anemia, as well as the nadir period, is more dramatic in preterm infants.
Infant growth and development are likely affected by hemoglobin levels, but current evidence is inconclusive regarding optimal hematocrit (Hct)/hemoglobin target levels.
Enteral iron supplementation of 2 to 4 mg/kg/day in the preterm infant leads to higher hemoglobin levels, improves iron stores, and lowers the risk of iron deficiency anemia, but its effect on neurodevelopment remains unclear. Erythropoiesis-stimulating agents are not routinely recommended because they are of limited benefit in reducing the number and volume of transfusions in preterm infants once strict transfusion criteria are used. However, their use may be associated with improved neurodevelopmental outcomes, and this is being addressed in ongoing clinical trials in preterm infants.
An association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC) has been reported in observational studies, but randomized controlled trials do not support a causal relationship.
I. HEMATOLOGIC PHYSIOLOGY OF THE NEWBORN. Significant changes occur in the red blood cell (RBC) mass of an infant during the neonatal period and ensuing months. The evaluation of anemia must take into account this developmental process as well as the infant’s physiologic needs.
A. Normal development: The physiologic anemia of infancy
1. In utero, the fetal aortic oxygen saturation is 45%, erythropoietin levels are high, and RBC production is rapid. The fetal liver is the major site of erythropoietin production.
2. After birth, the oxygen saturation is 95%, and erythropoietin is undetectable. RBC production by day 7 is <1/10th the level in utero. Reticulocyte counts are low, and the hemoglobin level falls (Table 45.1).
3. Despite dropping hemoglobin levels, the ratio of hemoglobin A to hemoglobin F increases, and the levels of 2,3-diphosphoglycerate (2,3-DPG)
(which interacts with hemoglobin A to decrease its affinity for oxygen, thereby enhancing oxygen release to the tissues) are high. As a result, oxygen delivery to the tissues actually increases. This physiologic “anemia” is not a functional anemia in that oxygen delivery to the tissues is adequate. Iron from degraded RBCs is stored.
(which interacts with hemoglobin A to decrease its affinity for oxygen, thereby enhancing oxygen release to the tissues) are high. As a result, oxygen delivery to the tissues actually increases. This physiologic “anemia” is not a functional anemia in that oxygen delivery to the tissues is adequate. Iron from degraded RBCs is stored.
Table 45.1. Hemoglobin Changes in Babies in the First Year of Life | |||||||||||||||||||||||||||||||||||||||
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4. At 8 to 12 weeks, hemoglobin levels reach their nadir (Table 45.2), oxygen delivery to the tissues is impaired, renal erythropoietin production is stimulated, and RBC production increases.
Table 45.2. Hemoglobin Nadir in Babies in the First Year of Life | |||||||||||||||
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5. Infants who have received transfusions in the neonatal period have lower nadirs than normal because of their higher percentage of hemoglobin A.
6. During this period of active erythropoiesis, iron stores are rapidly utilized. Iron stores are sufficient for 15 to 20 weeks in term infants. After this time, the hemoglobin level decreases if iron is not supplied.
B. Anemia of prematurity is an exaggeration of the normal physiologic anemia (see Tables 45.1 and 45.2).
1. RBC mass and iron stores are decreased because of low birth weight; however, hemoglobin concentrations are similar in preterm and term infants.
2. The hemoglobin nadir is reached earlier than in the term infant because of the following:
a. RBC survival is decreased in comparison with the term infant.
b. There is a relatively more rapid rate of growth in premature babies than in term infants. For example, a premature infant gaining 150 g per week requires approximately a 12 mL per week increase in total blood volume.
c. Many preterm infants have reduced red cell mass and iron stores because of iatrogenic phlebotomy for laboratory tests. This has been somewhat ameliorated with the use of microtechniques.
d. Vitamin E deficiency is common in small premature infants, unless the vitamin is supplied exogenously.
3. The hemoglobin nadir in premature babies is lower than in term infants because erythropoietin is produced by the term infant at a hemoglobin level of 10 to 11 g/dL but is produced by the premature infant at a hemoglobin level of 7 to 9 g/dL.
4. Iron administration before the age of 10 to 14 weeks does not increase the nadir of the hemoglobin level or diminish its rate of reduction. However, this iron is stored for later use.
5. Once the nadir is reached, RBC production is stimulated, and iron stores are rapidly depleted because less iron is stored in the premature infant than in the term infant.
II. ETIOLOGY OF ANEMIA IN THE NEONATE
A. Blood loss is manifested by a decreased or normal Hct, increased or normal reticulocyte count, and a normal bilirubin level (unless the hemorrhage is retained). If blood loss is recent (e.g., at delivery), the Hct and reticulocyte count may be normal, and the infant may be in shock. The Hct will fall later because of hemodilution. If the bleeding is chronic, the Hct will be low, the reticulocyte count up, and the baby normovolemic.
1. Obstetric causes of blood loss, including the following malformations of placenta and cord:
a. Abruptio placentae
b. Placenta previa
c. Incision of placenta at cesarean section
d. Rupture of anomalous vessels (e.g., vasa previa, velamentous insertion of cord, or rupture of communicating vessels in a multilobed placenta)
e. Hematoma of cord caused by varices or aneurysm
f. Rupture of cord (more common in short cords and in dysmature cords)
2. Occult blood loss
a. Fetomaternal bleeding may be chronic or acute. It occurs in 8% of all pregnancies, and in 1% of pregnancies, the volume may be as large as 40 mL. The diagnosis of this problem is by Kleihauer-Betke stain of maternal smear for fetal cells. Chronic fetal-to-maternal transfusion is suggested by a reticulocyte count >10%. Many conditions may predispose to this type of bleeding:
i. Placental malformations—chorioangioma or choriocarcinoma
ii. Obstetric procedures—traumatic amniocentesis, external cephalic version, internal cephalic version, breech delivery
iii. Spontaneous fetomaternal bleeding
b. Fetoplacental bleeding
i. Chorioangioma or choriocarcinoma with placental hematoma
ii. Cesarean section, with infant held above the placenta
iii. Tight nuchal cord or occult cord prolapse
c. Twin-to-twin transfusion
d. Twin anemia polycythemia sequence (TAPS), an uncommon form of chronic inter-twin transfusion between monochorionic twins characterized by large inter-twin hemoglobin differences in the absence of amniotic fluid discordance.
3. Bleeding in the neonatal period may be due to the following causes:
a. Intracranial bleeding associated with the following:
i. Prematurity
ii. Second twin
iii. Breech delivery
iv. Rapid delivery
v. Hypoxia
b. Massive cephalohematoma, subgaleal hemorrhage, or hemorrhagic caput succedaneum
c. Retroperitoneal bleeding
d. Ruptured liver or spleen
e. Adrenal or renal hemorrhage
f. Gastrointestinal bleeding (maternal blood swallowed from delivery or breast should be ruled out by the Apt test) (see Chapter 43)
i. Peptic ulcer
ii. NEC
iii. Nasogastric catheter
g. Bleeding from umbilicus
4. Iatrogenic causes. Excessive blood loss may result from blood sampling with inadequate replacement.
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