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

Anemia of Prematurity: Differential Diagnoses & Workup

Author: Charles F Potter, MD, Consulting Neonatologist, Newborn Care Physicians of Southeastern Wisconsin
Coauthor(s): W Michael Southgate, MD, Professor of Pediatrics, Pediatrics Program Director, Medical University of South Carolina
Contributor Information and Disclosures

Updated: Jan 15, 2009

Differential Diagnoses

Anemia, Acute
Parvovirus B19 Infection
Anemia, Chronic
Periventricular Hemorrhage-Intraventricular Hemorrhage
Birth Trauma
Head Trauma
Hemolytic Disease of Newborn

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.

More on Anemia of Prematurity

Overview: Anemia of Prematurity
Differential Diagnoses & Workup: Anemia of Prematurity
Treatment & Medication: Anemia of Prematurity
Follow-up: Anemia of Prematurity
References
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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. 2nd 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].

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  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].

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

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Further Reading

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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

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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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