eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Anemia of Prematurity

Charles F Potter, MD, Consulting Neonatologist, Newborn Care Physicians of Southeastern Wisconsin
W Michael Southgate, MD, Professor of Pediatrics, Pediatrics Program Director, Medical University of South Carolina

Updated: Jan 15, 2009

Introduction

Background

All infants experience a decrease in hemoglobin concentrations after birth, as the infant transitions from a relatively hypoxic state in utero to a relatively hyperoxic state in room air. Increased tissue oxygenation leads to a decline in erythropoietin (EPO) concentration and, for the term infant, a physiologic and usually asymptomatic anemia at age 8-12 weeks. Anemia of prematurity (AOP) is an exaggerated and pathologic response of the preterm infant to this transition. AOP is a normocytic, normochromic, hyporegenerative anemia that is characterized by the existence of a low serum EPO level in an infant who has what may be a remarkably reduced hemoglobin concentration.

Although the physiology and pathophysiology for AOP are well studied, controversy surrounds the timing, method, and effectiveness of therapeutic interventions for AOP. This article reviews the pathophysiology of AOP, the means of reducing its impact on premature infants, and its treatment through blood transfusion or recombinant EPO.

Pathophysiology

Inadequate RBC production

The first mechanism of anemia is inadequate RBC production for the growing premature infant. The location of EPO and RBC production changes during gestation of the fetus. EPO synthesis initially occurs in the fetal liver, with production gradually shifting to the kidney. By the end of gestation, the liver remains a major source of EPO.

In the first few weeks of embryogenesis, fetal erythrocytes are produced in the yolk sac. This site is succeeded by the fetal liver, which, by the end of the first trimester, has become the primary site of erythropoiesis. Bone marrow then begins to take on a more active role in producing erythrocytes. By approximately 32 weeks' gestation, the burden of erythrocyte production in the fetus is shared evenly between the liver and bone marrow. By 40 weeks' gestation, the marrow is the sole erythroid organ. Premature delivery does not accelerate the ontogeny of these processes.

Although EPO is not the only erythropoietic growth factor in the fetus, it is the most important. EPO is synthesized in response to both anemia and hypoxia. The degree of anemia and hypoxia required to stimulate EPO production is far greater for the fetal liver than for the fetal kidney. EPO production may not be stimulated until a hemoglobin concentration of 6-7 g/dL is reached. As a result, new RBC production in the extremely premature infant (whose liver remains the major site of EPO production) is blunted despite what may be marked anemia.

In addition, EPO, whether endogenously produced or exogenously administered, has a larger volume of distribution and is more rapidly eliminated by neonates, resulting in a curtailed time for bone marrow stimulation. Erythroid progenitors of premature infants are quite responsive to EPO when that growth factor finally is produced or administered, but the response may be blunted if iron stores are insufficient. Although the infant's response may produce increased EPO concentrations and reticulocyte counts, the infant's rapid growth may prevent the appropriate increase in hemoglobin concentration.

Shortened RBC life span or hemolysis

Secondly, the average life span of a neonatal RBC is only one half to two thirds that of the RBC life span in an adult. Cells of the most immature infants may survive only 35-50 days. The shortened RBC life span of the neonate is a result of multiple factors, including diminished levels of intracellular ATP, carnitine, and enzyme activity; increased susceptibility to lipid peroxidation; and increased susceptibility of the cell membrane to fragmentation.

Blood loss

Finally, blood loss may contribute to the development of AOP. If the neonate is held above the placenta for a time after delivery, a fetal-placental transfusion may occur. Conversely, delayed cord clamping may lessen the degree of AOP. More commonly, because of the need to closely monitor the tiny infant, frequent samples of blood are removed for various tests. These losses are often 5-10% of the total blood volume.

Taken together, the premature infant is at risk for the development of AOP because of limited synthesis during rapid growth, diminished RBC life span, and increased loss of RBCs.

Frequency

United States

Frequency of AOP is inversely related to the gestational age and/or birthweight of the population. As many as 50% of infants less than 32 weeks' gestational age develop symptoms as a result of AOP.

Mortality/Morbidity

Although a premature infant is unlikely to be allowed to become so severely anemic as to die, complications from necessary blood transfusions can ultimately be responsible for the death of a patient. Anemia is blamed for various signs and symptoms, including apnea, poor feeding, and inadequate weight gain (see History).

Race

Race has no influence on the incidence of AOP.

Sex

Although the presence of testosterone in the male infant is believed to be at least partially responsible for a slightly higher hemoglobin level at birth, this effect is of no significance with regard to individuals with AOP.

Age

The more immature the infant, the more likely the development of AOP. AOP is not typically a significant issue for infants born beyond 32 weeks' gestation. The nadir of the hemoglobin level is typically observed when the tiniest infants are aged 4-10 weeks, with concentrations of 8-10 g/dL if birthweight was 1200-1400 grams, or 6-9 g/dL if birthweight was less than 1200 grams.

AOP spontaneously resolves by the time most patients are aged 3-6 months.

Clinical

History

• Poor weight gain/difficulty feeding
• Apnea
• Tachypnea
• Decreased activity
• Pallor
• Tachycardia
• Flow murmurs

Physical

Debate regarding the presence or absence of physical findings in the infant with AOP is ongoing. Clinical trials designed to determine the efficacy of blood transfusions in relieving these findings have produced conflicting results.

• Poor growth
  • Inadequate weight gain despite adequate caloric intake is often attributed to AOP.
  • The response of weight gain to transfusions has been inconsistent in the literature.
• Apnea
  • If severe enough, anemia may result in respiratory depression manifested by increased periodic breathing and apnea.
  • Although some studies have demonstrated a decrease in frequency of these symptoms subsequent to blood transfusions, others have found similar results with simple crystalloid volume expansion.
• Decreased activity: Lethargy is frequently attributed to anemia, with subjective improvement subsequent to transfusion.
• Metabolic acidosis
  • Significant anemia can result in decreased oxygen-carrying capacity less than the needs of the tissue, resulting in increased anaerobic metabolism with production of lactic acid.
  • Blood transfusions have been documented to decrease lactic acid levels in otherwise healthy infants who are anemic and premature. Some medical professionals have suggested using lactate levels as an aid in determining the need for transfusion.
• Tachycardia
  • Infants with AOP may respond by increasing cardiac output through increased heart rates, presumably in response to inadequate oxygen delivery to the tissues caused by anemia.
  • Blood transfusions have been associated with a lowering of the heart rate in infants who are anemic.
• Tachypnea
• Flow murmurs

Causes

• AOP results from a combination of relatively diminished RBC production, shortened RBC life span, and blood loss (see Pathophysiology).
• Nutritional deficiencies of iron, vitamin E, vitamin B-12, and folate may exaggerate the degree of anemia.

Differential Diagnoses

Other Problems to Be Considered

Bone marrow infiltration
Diamond-Blackfan anemia
Disseminated intravascular coagulation
Elliptocytosis
G-6-PD deficiency
GI bleeding
Glucose kinase deficiency
Immune-mediated hemolysis
Iron deficiency
Pancytopenia
Spherocytosis
Twin-to-twin transfusion syndrome
Vitamin E deficiency

Workup

Laboratory Studies

The following studies are indicated when assessing anemia of prematurity (AOP):

• CBC count
  • The CBC count demonstrates normal WBC and platelet lines.
  • The hemoglobin is less than 10 g/dL but may descend to a nadir of 6-7 g/dL; the lowest levels are generally observed in the smallest infants.
  • RBC indices are normal (eg, normochromic, normocytic) for age.
• Reticulocyte count
  • The reticulocyte count is low when the degree of anemia is considered as a result of the low levels of erythropoietin (EPO). A rising reticulocyte count may not predict recovery from AOP.
  • The finding of an elevated reticulocyte count is not consistent with the diagnosis of AOP.
• Peripheral blood smear: No abnormal forms are observed.
• Maternal and infant blood typing: In the evaluation of anemia, consider the possibility of hemolytic processes, such as the ABO blood group system and Rh incompatibility.
• Direct antibody test (Coombs): This test may be coincidentally positive; however, with such a finding, ensure that an immune-mediated hemolytic process is not ongoing.
• Serum bilirubin: With an elevated serum bilirubin level, consider other possible explanations for the anemia. This would include hemolytic entities such as G-6-PD.

Treatment

Medical Care

The medical care options available to the clinician treating an infant with anemia of prematurity (AOP) are prevention, blood transfusion, recombinant erythropoietin (EPO) treatment or observation.

Prevention

• Reducing the amount of blood taken from the premature infant diminishes the need to replace blood. When caring for the premature infant, carefully consider the need for each laboratory study obtained. Hospitals that care for premature infants should have the ability to determine laboratory values using very small volumes of serum.
• Manufacturers are developing an array of technologies that require extremely small amounts of blood for a steadily increasing number of tests. Likewise, devices that allow blood gases and serum chemistries to be determined at bedside via an analyzer attached to the umbilical artery catheter without loss of blood have been developed. The impact of such devices on the development of anemia and/or the need for transfusions has yet to be determined.
• The use of noninvasive monitoring devices, such as transcutaneous hemoglobin oxygen saturation, partial pressure of oxygen, and partial pressure of carbon dioxide, may allow clinicians to decrease blood drawing; however, no data currently support such an impact of these devices.

Blood transfusion

• Packed red blood cell (PRBC) transfusions: Despite disagreement regarding timing and efficacy, PRBC transfusions continue to be the mainstay of therapy for the individual with AOP. The frequency of blood transfusions varies with gestational age, degree of illness, and, interestingly, the hospital evaluated. The decision to give a transfusion should not be made lightly because significant infectious, hematologic, immunologic, and metabolic complications are recognized. Late-onset necrotizing enterocolitis has been reported in stable-growing premature infants electively transfused for AOP. Transfusions also transiently decrease erythropoiesis and EPO levels, but this effect is not sustained.
• Reducing the number of transfusions: Studies derived from individual centers document a marked decrease in the administration of PRBC transfusions over the past 2 decades, even before the use of EPO. This decrease in transfusions is almost certainly multifactorial in origin. One frequently mentioned component is the adoption of transfusion protocols that take various factors into account, including hemoglobin levels, degree of cardiorespiratory disease, and traditional signs and symptoms of pathologic anemia. A restricted transfusion protocol may decrease the number of transfusions while also decreasing the hematocrit at discharge.
• The Premature Infant in Need of Transfusion (PINT) study demonstrated that transfusing infants to maintain a high hemoglobin level (8.5-13.5 g/dL) confers no benefit in terms of mortality, severe morbidity, or apnea intervention compared with infants transfused to maintain a low hemoglobin level (7.5-11.5 g/dL).¹ This differs from the Iowa study, which found less parenchymal brain hemorrhage, periventricular leukomalacia, and apnea in infants whose transfusion criteria was not restricted and whose hemoglobin level was higher. Clearly, no set guidelines for transfusion in infants with AOP are prescribed, and clinicians must determine a reasonable transfusion practice.
• Although transfusion guidelines are suggested to reduce the number of transfusions performed in a neonatal ICU (NICU), exact criteria or hemoglobin (Hb) and hematocrit (Hct) values at which to transfuse remain controversial. The Children's Hospital of Wisconsin Transfusion Committee uses the following clinical circumstances to review transfusions for infants:
  • An infant with a Hb level of less than 8 g/dL may be transfused at the discretion of the attending physician.
  • A stable infant with a Hb level of 8-10 g/dL without clinical evidence of anemia (tachycardia, tachypnea, poor feeding) or other exceptions listed below may be transfused.
  • An infant with a Hb level of 11-13 g/dL without a supplemental oxygen or continuous positive airway pressure (CPAP) requirement, apnea/bradycardia, significant tachycardia or tachypnea, or other exceptions listed below may be transfused.
  • An infant with a Hb level of more than 13 g/dL without an oxygen requirement of more than 40% by hood, CPAP, or ventilator; hypotension that requires pressor medication; major surgery; or other exceptions listed below may be transfused.
  • An infant with a Hb level of more than 15 g/dL without cyanotic heart disease, extracorporeal membrane oxygenation (ECMO) therapy, regional oxygen saturations less than 50%, or hypotension that requires pressor medications may be transfused.
  • An infant with a history of massive blood loss may be transfused at the discretion of the attending physician.

Observation

In infants who are asymptomatic, no longer acutely ill, and receiving adequate nutrition, including sufficient iron and other vitamins, observation may be the best course of action.

Reducing the number of donor exposures

In addition to reducing the number of transfusions, reducing the number of donor exposures is important. This can be accomplished as follows:

• Use PRBCs stored in preservatives (eg, citrate-phosphate-dextrose-adenine [CPDA-1]) and additive systems (eg, Adsol). Preservatives and additive systems allow blood to be stored safely for as long as 35-42 days. Infants may be assigned a specific unit of blood, which may suffice for treatment during their entire hospitalization and limit exposure to a single donor. Concerns that stored blood might increase serum potassium levels are unfounded, if the transfused volume is low.
• Use volunteer-donated blood and all available screening techniques. The risk of cytomegalovirus (CMV) transmission can be dramatically reduced (but not entirely) through the use of CMV-safe blood. This can be accomplished by using CMV serology-negative cells along with blood processed through leukocyte-reduction filters or inverted spin technique. These latter 2 methods also reduce other WBC-associated infectious agents (eg, Epstein-Barr virus, retroviruses, Yersinia enterocolitica) by yielding a leukocyte poor suspension of PRBCs. The American Red Cross is now providing exclusively leukocyte-reduced blood to hospitals in the United States.

Recombinant erythropoietin treatment

• Multiple investigations have established that premature infants respond to exogenously administered recombinant human EPO and supplemental iron with a brisk reticulocytosis. Subcutaneous administration of EPO may be preferred as intravenous administration has increased urinary losses. Although EPO cannot prevent early transfusions, modest decreases in the frequency of late PRBC transfusions have been documented. Additional iron supplementation is necessary during exogenous EPO treatment.
• Trials have evaluated the impact of EPO treatment in populations of the most immature neonates. These studies likewise have demonstrated that infants with VLBW are capable of responding to EPO with a reticulocytosis. Recent studies and a Cochrane Neonatal Systemic review suggest an association between exogenous EPO administration and retinopathy of prematurity.²  EPO with iron does not adversely affect growth or developmental outcomes, but the impact on the number of transfusions a premature infant receives ranges from nonexistent to small.
• At this time, no agreement regarding the safety, timing, dosing, route, or duration of therapy has been established. In short, the cost-benefit ratio for EPO has yet to be clearly established, and this medication is not universally accepted as a standard therapy for an infant with AOP.

Consultations

• Neonatology
• Pediatric hematology

Diet

• Provision of adequate amounts of vitamin E, vitamin B-12, folate, and iron are important to avoid exacerbating the expected decline in hemoglobin levels in the premature infant.

Medication

Growth factors

These agents are hormones that stimulate production of red cells from the erythroid tissues in the bone marrow.

Epoetin alfa (Epogen, Procrit)

Used to stimulate erythropoiesis and decrease the need for erythrocyte transfusions in high-risk preterm neonates. Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.
Infants require supplemental iron. Some physicians also use vitamin E and folate.

Dosing

Adult

Pediatric

200-400 U/kg/dose IV/SC for a total cumulative dose of 600-1400 U/kg/wk; if administered IV, give continuously or over at least 4 h

Interactions

None reported

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor with weekly CBC count for neutropenia and check for response; multidose vials contain benzyl alcohol

Vitamins and minerals

These are organic substances required by the body in small amounts for various metabolic processes. They are used clinically for the prevention and treatment of specific deficiency states.

Ferrous sulfate (PO)/Iron dextran (IV)

Nutritionally essential inorganic substance. Mainstay treatment for treating patients with iron deficiency anemia.

Dosing

Adult

Pediatric

PO: 2-4 mg/kg/d (based on elemental iron content); 6 mg/kg/d PO if infant is receiving Epoetin alpha;
IV: 0.4-1 mg/kg/d IV via continuous infusion

Supplemental dose should take into consideration the amount of iron the infant is receiving in the diet.

Interactions

Absorption is enhanced by ascorbic acid; interferes with tetracycline absorption; food and antacids impair absorption

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

May cause lethargy, hypotension, and GI upset including nausea, constipation, and erosion of gastric mucosa; may exacerbate vitamin E deficient hemolysis; iron toxicity can be fatal; parenteral (IV) administration may increase the risk of infection; allergic reactions and phlebitis may occur at infusion site

Vitamin E (Aquasol E, Aquavit E)

Protects polyunsaturated fatty acids in membranes from attack by free radicals and protects RBCs against hemolysis. Available as PO liquid drops (15 IU/0.3 mL).

Dosing

Adult

Pediatric

5-25 IU/d PO initially; measure plasma tocopherol within 1 wk and adjust dose accordingly

Interactions

Mineral oil decreases absorption; delays absorption of iron and increases effects of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Vitamin E may induce vitamin K deficiency; may increase the incidence of sepsis and necrotizing enterocolitis

Folic acid (Folvite)

Water-soluble vitamin used in nucleic acid synthesis. Required for normal erythropoiesis. Important cofactor for enzymes used in production of RBCs

Dosing

Adult

Pediatric

50 mcg/d PO

Interactions

Increase in seizure frequency and decrease in subtherapeutic levels of phenytoin reported when used concurrently

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Benzyl alcohol present in some products as preservative

Follow-up

Further Outpatient Care

• After discharge from the hospital, ensure regular determination of hematocrit levels in infants with anemia of prematurity (AOP).
• Once a steady increase in the hematocrit level has been established, only routine checks are required.

Inpatient & Outpatient Medications

• Administer and/or prescribe iron supplementation according to standard guidelines.

Transfer

• Transfer is generally not required unless transfusions cannot be carried out in the hospital's nursery.

Deterrence/Prevention

• Limit diagnostic blood draws to a minimum.

Complications

• Transfusion-acquired infections (eg, hepatitis, cytomegalovirus [CMV], human immunodeficiency virus [HIV], syphilis)
• Transfusion-associated fluid overload and electrolyte imbalances
• Transfusion-associated exposure to plasticizers
• Transfusion-associated hemolysis
• Posttransfusion graft versus host disease

Prognosis

• Spontaneous recovery in the individual with AOP occurs by age 3-6 months.

Patient Education

• Explain the normal course of anemia.
• Explain criteria for and risks of transfusions.
• Explain advantages and disadvantages of erythropoietin (EPO) administration.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider anemia as a possible cause of signs and symptoms
• Failure to notify the family about the patient's need for transfusion and obtain a consent before the transfusion
• Failure to consider the family's religious beliefs regarding transfusions
• Failure to anticipate transfusion-acquired infections and complications

References

1. [Best Evidence] Kirpalani H, Whyte RK, Andersen C, et al. The Premature Infants in Need of Transfusion (PINT) study: a randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr. Sep 2006;149(3):301-307. [Medline].

2. Ohlsson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004863. DOI: 10.1002/14651858.CD004863.pub2 [database online].

3. Al-Kharfy T, Smyth JA, Wadsworth L, et al. Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. J Pediatr. Jul 1996;129(1):89-96. [Medline].

4. [Best Evidence] Bell EF, Strauss RG, Widness JA, et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics. Jun 2005;115(6):1685-91. [Medline]. [Full Text].

5. Bowden RA, Slichter SJ, Sayers M, et al. A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant. Blood. Nov 1 1995;86(9):3598-603. [Medline].

6. Brown MS, Baron AE, France EK, Hamman RF. Association between higher cumulative doses of recombinant erythropoietin and risk for retinopathy of prematurity. J AAPOS. Apr 2006;10(2):143-9. [Medline].

7. Carbonell-Estrany X, Figueras-Aloy J, Alvarez E. Erythropoietin and prematurity--where do we stand?. J Perinat Med. 2005;33(4):277-86. [Medline].

8. Chen J, Smith LE. A double-edged sword: erythropoietin eyed in retinopathy of prematurity. J AAPOS. Jun 2008;12(3):221-2. [Medline].

9. DeMaio JG, Harris MC, Deuber C, Spitzer AR. Effect of blood transfusion on apnea frequency in growing premature infants. J Pediatr. Jun 1989;114(6):1039-41. [Medline].

10. Lachance C, Chessex P, Fouron JC, et al. Myocardial, erythropoietic, and metabolic adaptations to anemia of prematurity. J Pediatr. Aug 1994;125(2):278-82. [Medline].

11. Mally P, Golombek SG, Mishra R, et al. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. Nov 2006;23(8):451-8. [Medline].

12. Ohls RK. A multicenter randomized double-masked placebo-controlled trial of early erythropoietin and iron administration to preterm infants. Ped Res. 1999;45:1268.

13. Ohls RK. Developmental erythropoiesis. In: Polin RA, Fox WW, eds. Fetal and Neonatal Physiology. Vol 2. 2^nd ed. Philadelphia, Pa: WB Saunders Co; 1762-86.

14. Ohls RK, Ehrenkranz RA, Das A, et al. Neurodevelopmental outcome and growth at 18 to 22 months' corrected age in extremely low birth weight infants treated with early erythropoietin and iron. Pediatrics. Nov 2004;114(5):1287-91. [Medline]. [Full Text].

15. Ohls RK, Ehrenkranz RA, Wright LL, et al. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics. Oct 2001;108(4):934-42. [Medline]. [Full Text].

16. Ringer SA, Richardson DK, Sacher RA, et al. Variations in transfusion practice in neonatal intensive care. Pediatrics. Feb 1998;101(2):194-200. [Medline].

17. Romagnoli C, Zecca E, Gallini F, Girlando P, Zuppa AA. Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?. Eur J Pediatr. Aug 2000;159(8):627-8. [Medline].

18. Salsbury DC. Anemia of prematurity. Neonatal Netw. Aug 2001;20(5):13-20. [Medline].

19. Schwarz KB, Dear PR, Gill AB, et al. Effects of transfusion in anemia of prematurity. Pediatr Hematol Oncol. Oct-Nov 2005;22(7):551-9. [Medline].

20. Strauss RG. Controversies in the management of the anemia of prematurity using single-donor red blood cell transfusions and/or recombinant human erythropoietin. Transfus Med Rev. Jan 2006;20(1):34-44. [Medline].

21. Strauss RG. Erythropoietin in the pathogenesis and treatment of neonatal anemia. Transfusion. Jan 1995;35(1):68-73. [Medline].

22. Strauss RG. Practical issues in neonatal transfusion practice. Am J Clin Pathol. Apr 1997;107(4 Suppl 1):S57-63. [Medline].

23. Suk KK, Dunbar JA, Liu A, et al. Human recombinant erythropoietin and the incidence of retinopathy of prematurity: a multiple regression model. J AAPOS. Jun 2008;12(3):233-8. [Medline].

24. Ultee CA, van der Deure J, Swart J, Lasham C, van Baar AL. Delayed cord clamping in preterm infants delivered at 34 36 weeks' gestation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. Jan 2008;93(1):F20-3. [Medline].

25. Vamvakas EC, Strauss RG. Meta-analysis of controlled clinical trials studying the efficacy of rHuEPO in reducing blood transfusions in the anemia of prematurity. Transfusion. Mar 2001;41(3):406-15. [Medline].

26. Widness JA, Seward VJ, Kromer IJ, et al. Changing patterns of red blood cell transfusion in very low birth weight infants. J Pediatr. Nov 1996;129(5):680-7. [Medline].

27. Young TE, Mangum B. Neofax. Twenty-first edition. Montvale, NJ: Thomson Reuters; 2008.

Keywords

anemia of prematurity, AOP, erythropoietin, EPO, hemoglobin, red blood cell, hemolysis, blood loss, tachycardia, metabolic acidosis, respiratory depression, apnea, lactic acid, necrotizing enterocolitis, NEC, brain hemorrhage, periventricular leukomalacia, cytomegalovirus, CMV, Epstein-Barr virus, retroviruses, Yersinia enterocolitica

Contributor Information and Disclosures

Author

Charles F Potter, MD, Consulting Neonatologist, Newborn Care Physicians of Southeastern Wisconsin
Charles F Potter, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

W Michael Southgate, MD, Professor of Pediatrics, Pediatrics Program Director, Medical University of South Carolina
W Michael Southgate, MD is a member of the following medical societies: American Academy of Pediatrics and National Perinatal Association
Disclosure: Nothing to disclose.

Medical Editor

Scott MacGilvray, MD, Clinical Associate Professor of Pediatrics, East Carolina University School of Medicine
Scott MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association
Disclosure: MedImmune Speakers Bureau Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Brian S Carter, MD, FAAP, Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Co-director, Pediatric Advance Comfort Team, Monroe Carell Jr Children's Hospital at Vanderbilt
Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, National Hospice and Palliative Care Organization, and National Perinatal Association
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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