Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Postnatal diagnosis and management of hemolytic disease of the fetus and newborn

Darlene A Calhoun, DO
Section Editors
Donald H Mahoney, Jr, MD
Leonard E Weisman, MD
Deputy Editor
Melanie S Kim, MD


Hemolytic disease of the fetus and newborn (HDFN), also known as alloimmune HDFN or erythroblastosis fetalis, is caused by the destruction of red blood cells (RBCs) of the neonate or fetus by maternal immunoglobulin G (IgG) antibodies. These antibodies are produced when fetal erythrocytes, which express an RBC antigen not expressed in the mother, gain access to the maternal circulation.

The postnatal diagnosis and management of alloimmune HDFN in the newborn will be reviewed here. The prenatal diagnosis and management of HDFN are discussed separately. (See "Management of non-Rhesus (D) red blood cell alloantibodies during pregnancy" and "Overview of Rhesus D alloimmunization in pregnancy".)


Alloimmune HDFN primarily involves the major blood groups of Rhesus (Rh), A, B, AB, and O, although minor blood group incompatibilities (Kell, Duffy, MNS, P, and Diego systems) can also result in significant disease (table 1) [1]. Because of the low frequency of HDFN due to the minor blood groups, they are not presented in detail as part of this review. (See "Red blood cell antigens and antibodies".)

Only maternal immunoglobulin G (IgG) causes HDFN, because transfer of maternal antibodies across the placenta depends upon the fragment crystallizable (Fc) component of the IgG molecule, which is not present in immunoglobulin A (IgA) and immunoglobulin M (IgM). (See "Structure of immunoglobulins", section on 'Antibody fragments'.)

Rh(D) hemolytic disease — Individuals are classified as Rhesus (Rh) negative or positive based upon the expression of the major D antigen on the erythrocyte. The original description of HDFN was due to Rh(D) incompatibility, which is associated with the most severe form of the disease (hydrops fetalis).

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 25, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Ross ME, Waldron PE, Cashore WJ, de Alarcon PA. Hemolytic disease of the fetus and newborn. In: Neonatal Hematology: Pathogenesis, Diagnosis, and Management of Hematologic Problems, 2nd ed, de Alacon PA, Werner EJ, Christensen RD (Eds), Cambridge University Press, Cambridge 2013. p.65.
  2. Ozolek JA, Watchko JF, Mimouni F. Prevalence and lack of clinical significance of blood group incompatibility in mothers with blood type A or B. J Pediatr 1994; 125:87.
  3. McDonnell M, Hannam S, Devane SP. Hydrops fetalis due to ABO incompatibility. Arch Dis Child Fetal Neonatal Ed 1998; 78:F220.
  4. McKenzie, S. Anemia. In: Intensive Care of the Fetus and Newborn, 2nd edition, Spitzer AR (Ed), Elsevier Mosby, 2005. p.1289.
  5. Bakkeheim E, Bergerud U, Schmidt-Melbye AC, et al. Maternal IgG anti-A and anti-B titres predict outcome in ABO-incompatibility in the neonate. Acta Paediatr 2009; 98:1896.
  6. Özgönenel B, Kukreja G, O'Malley B, Bluth MH. Neonatal BO Incompatibility Is Associated With a Positive Cord Blood Direct Antiglobulin Test in Infants of Black Ethnicity. J Pediatr Hematol Oncol 2015; 37:e453.
  7. Lamba DS, Kaur R, Basu S. Clinically Significant Minor Blood Group Antigens amongst North Indian Donor Population. Adv Hematol 2013; 2013:215454.
  8. Dean L. The Rh Blood Group. In: Blood Groups and Red Cell Antigens, National Center for Biotechnology Information (US), Bethesda, MD 2005.
  9. Paterakis GS, Lykopoulou L, Papassotiriou J, et al. Flow-cytometric analysis of reticulocytes in normal cord blood. Acta Haematol 1993; 90:182.
  10. Desjardins L, Blajchman MA, Chintu C, et al. The spectrum of ABO hemolytic disease of the newborn infant. J Pediatr 1979; 95:447.
  11. Cord Blood Direct Antiglobulin Testing. www.clinlabnavigator.com/cord-blood-direct-antiglobulin-testing.html (Accessed on July 06, 2016).
  12. Valsami S, Politou M, Boutsikou Τ, et al. Importance of Direct Antiglobulin Test (DAT) in Cord Blood: Causes of DAT (+) in a Cohort Study. Pediatr Neonatol 2015; 56:256.
  13. Maisels, MJ. Jaundice. In: Avery's Neonatology: Pathophysiology and Management of the Newborn, McDonald, MG, Mullett, MD, Seshia, MM (Eds), Lippincott, Williams & Williams, Philadelphia 2005. p.800.
  14. Peterec SM. Management of neonatal Rh disease. Clin Perinatol 1995; 22:561.
  15. Wyckoff MH, Aziz K, Escobedo MB, et al. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132:S543.
  16. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114:297.
  17. Calhoun DA, Christensen RD, Edstrom CS, et al. Consistent approaches to procedures and practices in neonatal hematology. Clin Perinatol 2000; 27:733.
  18. Lakatos L, Csáthy L, Nemes E. "Bloodless" treatment of a Jehovah's Witness infant with ABO hemolytic disease. J Perinatol 1999; 19:530.
  19. Arndt PA, Garratty G, Daniels G, et al. Late onset neonatal anaemia due to maternal anti-Ge: possible association with destruction of eythroid progenitors. Transfus Med 2005; 15:125.
  20. Dhodapkar KM, Blei F. Treatment of hemolytic disease of the newborn caused by anti-Kell antibody with recombinant erythropoietin. J Pediatr Hematol Oncol 2001; 23:69.
  21. Ohls RK. The use of erythropoietin in neonates. Clin Perinatol 2000; 27:681.
  22. Mainie P. Is there a role for erythropoietin in neonatal medicine? Early Hum Dev 2008; 84:525.
  23. Wacker P, Ozsahin H, Stelling MJ, Humbert J. Successful treatment of neonatal rhesus hemolytic anemia with high doses of recombinant human erythropoietin. Pediatr Hematol Oncol 2001; 18:279.
  24. Ovali F, Samanci N, Dağoğlu T. Management of late anemia in Rhesus hemolytic disease: use of recombinant human erythropoietin (a pilot study). Pediatr Res 1996; 39:831.
  25. Pessler F, Hart D. Hyporegenerative anemia associated with Rh hemolytic disease: treatment failure of recombinant erythropoietin. J Pediatr Hematol Oncol 2002; 24:689.
  26. Grundbacher FJ. The etiology of ABO hemolytic disease of the newborn. Transfusion 1980; 20:563.
  27. Blanchette, V, Dror, et al. Hematology. In: Avery's Neonatology: Pathophysiology and Management of the Newborn, McDonald, MG, Mullett, MD, Seshia, MM (Eds), Lippincott, Williams & Williams, Philadelphia 2005. p.1169.
  28. Wennberg RP, Depp R, Heinrichs WL. Indications for early exchange transfusion in patients with erythroblastosis fetalis. J Pediatr 1978; 92:789.
  29. Sato K, Hara T, Kondo T, et al. High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility. Acta Paediatr Scand 1991; 80:163.
  30. Wagner T, Resch B, Legler TJ, et al. Severe HDN due to anti-Ce that required exchange tranfusion. Transfusion 2000; 40:571.
  31. Gottstein R, Cooke RW. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2003; 88:F6.
  32. Rübo J, Albrecht K, Lasch P, et al. High-dose intravenous immune globulin therapy for hyperbilirubinemia caused by Rh hemolytic disease. J Pediatr 1992; 121:93.
  33. Hammerman C, Kaplan M, Vreman HJ, Stevenson DK. Intravenous immune globulin in neonatal ABO isoimmunization: factors associated with clinical efficacy. Biol Neonate 1996; 70:69.
  34. Alpay F, Sarici SU, Okutan V, et al. High-dose intravenous immunoglobulin therapy in neonatal immune haemolytic jaundice. Acta Paediatr 1999; 88:216.
  35. Dağoğlu T, Ovali F, Samanci N, Bengisu E. High-dose intravenous immunoglobulin therapy for rhesus haemolytic disease. J Int Med Res 1995; 23:264.
  36. Alcock GS, Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates. Cochrane Database Syst Rev 2002; :CD003313.
  37. Louis D, More K, Oberoi S, Shah PS. Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: an updated systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2014; 99:F325.
  38. Zimring JC, Welniak L, Semple JW, et al. Current problems and future directions of transfusion-induced alloimmunization: summary of an NHLBI working group. Transfusion 2011; 51:435.
  39. BOWMAN JM. Gastrointestinal absorption of isohemagglutinin. Am J Dis Child 1963; 105:352.