May 24, 2012 - placenta-dependent, relatively hypoxic, intrauterine environ- ment into the ... ruptured placental vessels related to vasa previa or velamentous.
This article was downloaded by: [Sandra Juul] On: 12 August 2015, At: 19:28 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: 5 Howick Place, London, SW1P 1WG
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Erythropoiesis and the approach to anemia in premature infants Sandra Juul
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Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, WA, USA Published online: 24 May 2012.
To cite this article: Sandra Juul (2012) Erythropoiesis and the approach to anemia in premature infants, The Journal of Maternal-Fetal & Neonatal Medicine, 25:sup5, 97-99 To link to this article: http://dx.doi.org/10.3109/14767058.2012.715467
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The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(S5): 97–99 © 2012 Informa UK, Ltd. ISSN 1476-7058 print/ISSN 1476-4954 online DOI: 10.3109/14767058.2012.715467
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Erythropoiesis and the approach to anemia in premature infants Sandra Juul
Downloaded by [Sandra Juul] at 19:28 12 August 2015
Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, WA, USA and (3) inappropriately low circulating erythropoietin concentration for the degree of anemia. While anemia of prematurity contributes to the anemia encountered in essentially all extremely low birth weight infants, there usually are other important contributing factors. These factors are often more significant than anemia of prematurity. Contributing factors include: phlebotomy losses, iron or other nutritional deficiencies, inflammation, and chronic illness. Normal developmental processes also contribute. The following paragraphs will outline factors that influence the development of anemia in newborns.
Objective: To review causes of anemia in preterm infants and to suggest potential preventive measures. Methods: Data for this review is obtained from review of the literature. Results: An approach to investigating and treating causes of neonatal anemia is outlined. Conclusions: Clinical practices can significantly impact anemia in premature infants. Delayed cord clamping, decreasing phlebotomy loss and optimizing nutritional support are practices that may decrease the severity of anemia, thereby decreasing the need for transfusions or erythropoietin treatment. Keywords: Hct, neonate, preterm Erythropoiesis, “Erythro” (red) – “poiesis” (growth) describes the process of red blood cell (RBC) production. During embryonic development, two types of RBCs are formed by distinct processes. The first, termed primitive erythropoiesis, results in nucleated RBCs. This process is not dependent on the presence of erythropoietin (Epo), and cannot sustain life. Primitive RBCs are large (>20 µm), CD34-negative, and contain predominantly embryonic hemoglobin. Definitive erythropoiesis begins later in development, is Epo-dependent, and results in smaller enucleated, CD34+ erythroblasts, which produce fetal and adult hemoglobins (Hb). Primitive erythroblasts undergo apoptosis, becoming extinct during fetal life, whereas definitive erythroblasts are able to selfrenew [1]. While Epo is not essential for primary erythropoiesis, it is the primary growth factor supporting definitive erythropoiesis: in the absence of Epo signaling (Epo and Epo receptor null mutation mice), definitive erythropoiesis does not occur, and the embryos die at embryonic day 13.5 due to severe anemia [2].
Factors contributing to anemia in preterm infants Transitional physiology Physiologic changes occur as the fetus transitions from the placenta-dependent, relatively hypoxic, intrauterine environment into the in the lung-dependent, oxygen-rich, environment. A major stimulus to Epo production is tissue hypoxia, mediated through HIF-1 production. As the fetus transitions from the hypoxic intrauterine environment to the oxygen-rich postnatal environment, Epo production is downregulated. Another contributing factor to low Epo production is the transition of Epo production from the liver to the kidney. This transition occurs during the first 3–4 months past term birth. When a child is born prematurely, this transition still occurs based on a postconceptional time clock. This is an important contributor to anemia of prematurity because the liver is less sensitive to tissue hypoxia as a stimulus for Epo production than the kidney. This postnatal decrease in Epo production translates into a 20% decrease in erythroid progenitor cells in the marrow. Epo clearance and volume of distribution is also high in neonates relative to adults, and this likely contributes to low circulating concentrations. The fact that erythrocyte progenitors are quite sensitive to Epo, and endogenous Epo production is low, forms part of the rationale for Epo treatment of anemia of prematurity.
Physiologic anemia In the 3 months following birth, the hematocrit (Hct) and Hb of all newborns decreases [3]. In healthy term infants, this decrease is physiologic and they remain asymptomatic. The nadir Hct in term infants occurs between 10 and 12 weeks of age, and rarely falls below 30% with Hb concentrations of 10–12 g/dL. After 10–12 weeks, the Hct and Hb increase slowly to reach adult values by 2 years of age. In preterm infants, the drop in Hct and Hb is more rapid and more severe. The nadir Hct occurs between 4 and 6 weeks of age, with Hct values of 21–28% seen commonly in infants with birth weights less than 1.0 kg and less than 1.5 kg, respectively. This level of anemia is due to a combination of physiologic factors (decrease in Epo production) and nonphysiologic factors such as iatrogenic blood loss for laboratory testing and iron deficiency. The smaller and more immature the baby, the more severe the anemia is likely to be. Anemia of prematurity is defined as: (1) Anemia in a preterm infant
