Physiologic Anemia of Infancy

Published on 22/03/2015 by admin

Filed under Pediatrics

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 5784 times

Chapter 447 Physiologic Anemia of Infancy

Norma B. Lerner

At birth, normal full-term infants have higher hemoglobin and hematocrit levels and larger red blood cells (RBCs) than do older children and adults. However, within the 1st wk of life, a progressive decline in hemoglobin level begins and then persists for 6-8 wk. The resulting anemia is known as the physiologic anemia of infancy. Several factors appear to be involved.

With the onset of respiration at birth, considerably more oxygen becomes available for binding to hemoglobin, and, as a consequence, the hemoglobin-oxygen saturation increases from 50% to 95% or more. There is also a gradual, normal developmental switch from fetal to adult hemoglobin synthesis after birth that results in the replacement of high-oxygen-affinity fetal hemoglobin with lower-affinity adult hemoglobin, capable of delivering more oxygen to tissues. The increase in blood oxygen content and delivery results in the downregulation of erythropoietin (EPO) production, leading to suppression of erythropoiesis. Because there is no erythropoiesis, aged RBCs that are removed from the circulation are not replaced and the hemoglobin level decreases. The hemoglobin concentration continues to decline until tissue oxygen needs become greater than oxygen delivery. Normally, this point is reached between 8 and 12 wk of age, when the hemoglobin concentration is about 11 g/dL. At this juncture, EPO production increases and erythropoiesis resumes. The supply of stored reticuloendothelial iron, derived from previously degraded RBCs, remains sufficient for this renewed hemoglobin synthesis, even in the absence of dietary iron intake, until approximately 20 wk of age. In all, this “anemia” should be viewed as a physiologic adaptation to extrauterine life, reflecting the excess oxygen delivery relative to tissue oxygen requirements. There is no hematologic problem, and no therapy is required.

Premature infants also develop a physiologic anemia, known as physiologic anemia of prematurity. The hemoglobin decline is both more extreme and more rapid. Minimal hemoglobin levels of 7-9 g/dL commonly are reached by 3-6 wk of age, and levels may be even lower in very small premature infants (Chapter 97). The same physiologic factors at play in term infants are operative in preterm infants but are exaggerated. In premature infants, the physiologic hemoglobin decline may be intensified by blood loss from repeated phlebotomies obtained to monitor ill neonates. Demands on erythropoiesis are further heightened by the premature infant’s shortened RBC lifespan (40-60 days) and the accelerated expansion of RBC mass that accompanies the premature baby’s rapid rate of growth. Nonetheless, plasma EPO levels are lower than would be expected for the degree of anemia, resulting in a suboptimal erythropoietic response. The reason for diminished EPO levels is not fully understood. During fetal life, EPO synthesis is handled primarily by the liver, whose oxygen sensor is relatively insensitive to hypoxia when compared to the oxygen sensor of the kidney. The developmental switch from liver to kidney EPO production is not accelerated by early birth, and thus the preterm infant must rely on the liver as the primary site for synthesis, leading to diminished responsiveness to anemia. An additional mechanism thought to contribute to diminished EPO levels may be accelerated EPO metabolism.

Physiologic anemia of infancy may be exacerbated by other ongoing processes. A late hyporegenerative anemia, with absence of reticulocytes, can occur in infants with mild hemolytic disease of the newborn. The persistence of maternally derived anti-RBC antibodies in the infant’s circulation can lead to an ongoing low-grade hemolytic anemia that can exaggerate the physiologic anemia. Lower-than-expected hemoglobin at the “physiologic” nadir has also been seen in infants after intrauterine or neonatal RBC transfusions. When infants are transfused with adult blood containing HbA, the associated shift of the oxygen dissociation curve facilitates oxygen delivery to the tissues. Accordingly, the definition of anemia and the need for transfusion should be based not only on the infant’s hemoglobin level but also oxygen requirements and the ability of circulating RBCs to release oxygen to the tissues.

Some dietary factors, such as folic acid deficiency, can aggravate physiologic anemia. Unless there has been significant blood loss, iron stores should be sufficient to maintain erythropoiesis early on. Notably, despite past suggestions to the contrary, vitamin E deficiency does not appear to play a role in anemia of prematurity. A controlled and blinded study of oral administration of vitamin E to infants weighing <1,500 g showed no difference in hemoglobin levels, reticulocytes, RBC morphology, or platelet counts. Breast milk and modern infant formulas appear to provide adequate vitamin E.

Treatment

In the full-term infant, physiologic anemia requires no therapy beyond ensuring that the infant’s diet contains essential nutrients for normal hematopoiesis. In premature infants an optimal hematocrit has not been established and is usually dictated by the infant’s overall clinical condition. Transfusions may be needed to maintain the hematocrit at what is considered safe for that child. Premature infants who are feeding well and growing normally rarely need transfusion unless iatrogenic blood loss has been significant. Although factors such as poor weight gain, respiratory difficulties, and abnormal heart rate have prompted transfusion, the beneficial effect has not been documented. Laboratory tests such as blood lactate, erythropoietin, and mixed venous oxygen saturation have poor predictive value. Liberal and restrictive transfusion strategies have been compared in this population. Although a restrictive strategy did not result in increased morbidity or mortality, it might have resulted in poorer neuroprotection than that provided by a liberal approach. For now, most consensus-based transfusion guidelines advise the liberal approach. When transfusions are necessary, an RBC volume of 10-15 mL/kg is recommended. It is good practice to split units derived from a single donor so that sequential transfusions can be given as required and donor exposure can be minimized. In early preterm infants (<1,250 g), the half-life of transfused RBCs is about 30 days.

Because premature infants are known to have low plasma erythropoietin levels, recombinant human erythropoietin (rEPO) has been studied as an alternative to transfusion for the treatment of symptomatic preterm infants with anemia of prematurity. Infants have been shown to require higher dosages per kilogram than adults and supplementation with adequate protein, vitamin E, and iron to achieve the full benefit of the medication. Although rEPO has been associated with reduced numbers of red cell transfusions, it is unclear whether it reliably reduces donor exposures. Reports of adverse effects such as a possible increase in retinopathy of prematurity have further limited a willingness to use this expensive treatment. Its routine use in this population might have to await further clinical trials.

Bibliography

Bednarek FJ, Weisberger S, Richardson DK, et al. Variations in blood transfusions among newborn intensive care units. J Pediatr. 1998;133:601-607.

Bell EF, Strauss RG, Widness, et al. Randomized trial of liberal versus restrictive guidelines for red cell transfusion in preterm infants. Pediatrics. 2005;115:1685-1691.

Fain J, Hilsenrath P, Widness JA, et al. A cost analysis comparing erythropoietin and red cell transfusions in the treatment of anemia of prematurity. Transfusion. 1995;35:936-943.

Kirpalani H, Whyte RK, Anderson C, et al. The premature infants in need of transfusion (PINT) study: a randomized, controlled trial of restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. 2006;149:301-307.

Meyer MP, Haworth C, Meyer JH. A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin. J Pediatr. 1996;129:258-263.

Ohls RK. The use of erythropoietin in neonates. Clin Perinatol. 2000;27:681-696.

Strauss GR. How I transfuse red cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion. 2008;48:209-217.

Von Kohorn I, Ehrenkranz RA. Anemia in the preterm infant: erythropoietin versus erythrocyte transfusion—it’s not that simple. Clin Perinatol. 2009;36:111-123.

Related posts:

Disorders of the Complement System Default ThumbnailGynecologic Care for Girls with Special Needs Cardiac Development Hypothyroidism Cystic Diseases of the Biliary Tract and Liver Vesicoureteral Reflux