Hemolytic Disease of the Newborn Questions & Answers

1. Bowman JM. Hemolytic disease (erythroblastosis fetalis). Creasy RK, Resnik R. Maternal-fetal medicine. 4th edition. Philadelphia: WB Saunders; 1999. 736-767.

2. [Guideline] Snyder EL, Lipton KS. Prevention of hemolyic disease of the newborn due to anti-D Prenatal/perinatal testing and Rh immune globulin administration. American Association of Blood Banks Association Bulletin. 1998. 98:1-6.

3. Fasano RM. Hemolytic disease of the fetus and newborn in the molecular era. Semin Fetal Neonatal Med. 2015 Nov 14. [QxMD MEDLINE Link].

4. van der Schoot CE, Tax GH, Rijnders RJ, de Haas M, Christiaens GC. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed. Transfus Med Rev. 2003 Jan. 17(1):31-44. [QxMD MEDLINE Link].

5. Singleton BK, Green CA, Avent ND, et al. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype. Blood. 2000 Jan 1. 95(1):12-8. [QxMD MEDLINE Link].

6. Flegel WA. Molecular genetics and clinical applications for RH. Transfus Apher Sci. 2011 Feb. 44(1):81-91. [QxMD MEDLINE Link]. [Full Text].

7. Cruz-Leal Y, Marjoram D, Lazarus AH. Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?. Curr Opin Hematol. 2017 Nov. 24 (6):536-43. [QxMD MEDLINE Link].

8. Moise KJ. Hemolytic disease of the fetus and newborn. Creasy RK, Resnik R. Maternal-fetal Medicine: Principles and Practice. 6th ed. Philadelphia: WB Saunders; 2008. 477-503.

9. Kaplan M, Na'amad M, Kenan A, et al. Failure to predict hemolysis and hyperbilirubinemia by IgG subclass in blood group A or B infants born to group O mothers. Pediatrics. 2009 Jan. 123(1):e132-7. [QxMD MEDLINE Link].

10. Luchtman-Jones L, Schwartz AL, Wilson DB. The blood and hematopoietic system. Fanaroff AA, Martin RJ, eds. Neonatal-Perinatal Medicine-Diseases of the Fetus and Infant. 8th ed. St. Louis, Mo: Mosby; 2006. Vol 2: 1287-1356.

11. Mentzer, WC, Glader BE. Erythrocyte Disorders in Infancy. Taeusch HW, Ballard RA eds. Avery's Diseases of the Newborn. 8th Edition. Philadelphia, PA: Elsevier Saunders; 2005. 1180-1214.

12. McCarthy WA, Popek EJ. Persistence of villous immaturity in term deliveries following intrauterine transfusion for Parvovirus B19 infection and RhD-associated hemolytic disease of the fetus and newborn. Pediatr Dev Pathol. 2017 Nov-Dec. 20 (6):469-74. [QxMD MEDLINE Link].

13. Delaney M, Matthews DC. Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn. Hematology Am Soc Hematol Educ Program. 2015 Dec 5. 2015 (1):146-51. [QxMD MEDLINE Link].

14. Chavez GF, Mulinare J, Edmonds LD. Epidemiology of Rh hemolytic disease of the newborn in the United States. JAMA. 1991 Jun 26. 265(24):3270-4. [QxMD MEDLINE Link].

15. Eder AF. Update on HDFN: new information on long-standing controversies. Immunohematol. 2006. 22(4):188-95. [QxMD MEDLINE Link].

16. Hudon L, Moise KJ Jr, Hegemier SE, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for the treatment of fetal hemolytic disease. Am J Obstet Gynecol. 1998 Oct. 179(4):858-63. [QxMD MEDLINE Link].

17. Lindenburg IT, Smits-Wintjens VE, van Klink JM, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am J Obstet Gynecol. 2012 Feb. 206(2):141.e1-8. [QxMD MEDLINE Link].

18. Gruslin-giroux A, Moore TR. Erythroblastosis Fetalis. Fanaroff AA, Martin RJ. Neonatal-Perinatal Medicine. 8th edition. St. Louis, MO: Mosby-year book Inc; 2006. Vol 1: 389-408.

19. Smits-Wintjens VE, Rath ME, van Zwet EW, et al. Neonatal morbidity after exchange transfusion for red cell alloimmune hemolytic disease. Neonatology. 2013. 103(2):141-7. [QxMD MEDLINE Link].

20. Moise KJ Jr. Red blood cell alloimmunization in Pregnancy. Seminars in Hematology. 2005. 42:169-178.

21. Harkness UF, Spinnato JA. Prevention and management of RhD isoimmunization. Clin Perinatol. 2004 Dec. 31(4):721-42, vi. [QxMD MEDLINE Link].

22. Pirelli KJ, Pietz BC, Johnson ST, Pinder HL, Bellissimo DB. Molecular determination of RHD zygosity: predicting risk of hemolytic disease of the fetus and newborn related to anti-D. Prenat Diagn. 2010 Dec. 30(12-13):1207-12. [QxMD MEDLINE Link].

23. Bianchi DW, Avent ND, Costa JM, van der Schoot CE. Noninvasive prenatal diagnosis of fetal Rhesus D: ready for Prime(r) Time. Obstet Gynecol. 2005. 106(4):841-4. [QxMD MEDLINE Link].

24. Rouillac-Le Sciellour C, Puillandre P, Gillot R, et al. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004. 8(1):23-31. [QxMD MEDLINE Link].

25. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. 2008 Jul. 112(1):164-76. [QxMD MEDLINE Link].

26. Liley AW. Liquor amnii analysis in management of pregnancy complicated by rhesus immunization. Am J Obstet Gynecol. 1961. 82:1359-71.

27. Bowman JM, Pollock JM. Amniotic fluid spectrophotometry and early delivery in the management of erythroblastosis fetalis. Pediatr. 1965 May. 35:815-835. [QxMD MEDLINE Link].

28. Nicolaides KH, Rodeck CH, Mibashan RS, Kemp JR. Have Liley charts outlived their usefulness?. Am J Obstet Gynecol. 1986 Jul. 155(1):90-4. [QxMD MEDLINE Link].

29. Queenan JT, Tomai TP, Ural SH, King JC. Deviation in amniotic fluid optical density at a wavelength of 450 nm in Rh-immunized pregnancies from 14 to 40 weeks' gestation: a proposal for clinical management. Am J Obstet Gynecol. 1993 May. 168(5):1370-6. [QxMD MEDLINE Link].

30. Scott F, Chan FY. Assessment of the clinical usefulness of the "Queenan" chart versus the "Liley" chart in predicting severity of rhesus iso-immuinization. Prenat Diagn. (11) 1998. 18:1143-48. [QxMD MEDLINE Link].

31. Oepkes D, Seaward PG, Vandenbussche FP, Windrim R, Kingdom J, Beyene J. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med. 2006 Jul 13. 355(2):156-164. [QxMD MEDLINE Link].

32. Brojer E, Husebekk A, Dębska M, et al. Fetal/neonatal alloimmune thrombocytopenia: pathogenesis, diagnostics and prevention. Arch Immunol Ther Exp (Warsz). 2015 Nov 12. [QxMD MEDLINE Link].

33. Koenig JM. Evaluation and treatment of erythroblastosis fetalis in the neonate. Christensen R, ed. Hematologic Problems of the Neonate. Philadelphia, Pa: WB Saunders; 2000. 185-207.

34. Wang WH, Xu D, Han YM, Yang ZJ. [Risk factors for early disseminated intravascular coagulation in neonates with sepsis] [Chinese]. Zhongguo Dang Dai Er Ke Za Zhi. 2015 Apr. 17 (4):341-4. [QxMD MEDLINE Link].

35. Christensen RD, Henry E. Hereditary spherocytosis in neonates with hyperbilirubinemia. Pediatrics. 2010 Jan. 125(1):120-5. [QxMD MEDLINE Link].

36. Vidnes J, Finne H. Immunoreactive insulin in amniotic fluid from Rh-immunized women. Biol Neonate. 1977. 31(1-2):1-6. [QxMD MEDLINE Link].

37. Romano EL, Hughes-Jones NC, Mollison PL. Direct antiglobulin reaction in ABO-haemolytic disease of the newborn. Br Med J. 1973 Mar 3. 1(852):524-6. [QxMD MEDLINE Link].

38. Murray NA, Roberts IA. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2007 Mar. 92(2):F83-8. [QxMD MEDLINE Link].

39. 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 Dec. 98(12):1896-901. [QxMD MEDLINE Link].

40. Peeters B, Geerts I, Badts AM, Saegeman V, Moerman J. Usefulness of maternal red cell antibodies to predict hemolytic disease of the fetus and newborn and significant neonatal hyperbilirubinemia: a retrospective study. Clin Chem Lab Med. 2017 Aug 28. 55 (9):e202-e205. [QxMD MEDLINE Link].

41. Zwiers C, van Kamp I, Oepkes D, Lopriore E. Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome. Expert Rev Hematol. 2017 Apr. 10 (4):337-344. [QxMD MEDLINE Link].

42. Lozar-Krivec J, Bratanic B, Paro-Panjan D. The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization. J Matern Fetal Neonatal Med. 2016 Feb. 29 (3):452-6. [QxMD MEDLINE Link].

43. Madan, A, MacMahon JR, Stevenson DK. Neonatal hyperbilirubinemia. Taeusch HW, Ballard RA, eds. Avery’s Diseases of The Newborn. 8th ed. Philadelphia, Pa: Elsevier Saunders; 2005. 1226-1256.

44. [Guideline] Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul. 114(1):297-316. [QxMD MEDLINE Link].

45. Martin CR, Cloherty JP. Neonatal Hyperbilirubinemia. Cloherty JP, Eichenwald EC, Stark AR. Manual of Neonatal Care. 5th Edition. Philadelphia: Lippincott Williams and Wilkins; 2004. 181-212.

46. Li M, Blaustein JC. Persistent hemolytic disease of the fetus and newborn (HDFN) associated with passive acquisition of anti-D in maternal breast milk. Transfusion. 2017 Sep. 57 (9):2121-24. [QxMD MEDLINE Link].

47. Wong RJ, DeSandre GH, Stevenson DK. Neonatal jaundice and liver disease. Fanaroff AA, Martin RJ. Neonatal-Perinatal Medicine: Diseases of the fetus and Infant. 7th edition. St. Louis, MO: Mosby-year book Inc; 2002. Vol 2: 1419-11466.

48. Peterec SM. Management of neonatal Rh disease. Clin Perinatol. 1995 Sep. 22(3):561-92. [QxMD MEDLINE Link].

49. Hammerman C, Vreman HJ, Kaplan M, Stevenson DK. Intravenous immune globulin in neonatal immune hemolytic disease: does it reduce hemolysis?. Acta Paediatr. 1996 Nov. 85(11):1351-3. [QxMD MEDLINE Link].

50. Elalfy MS, Elbarbary NS, Abaza HW. Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial. Eur J Pediatr. 2011 Apr. 170(4):461-7. [QxMD MEDLINE Link].

51. Elalfy MS, Elbarbary NS, Abaza HW. Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial. Eur J Pediatr. 2011 Apr. 170(4):461-7. [QxMD MEDLINE Link].

52. Smits-Wintjens VE, Walther FJ, Rath ME, et al. Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial. Pediatrics. 2011 Apr. 127(4):680-6. [QxMD MEDLINE Link].

53. Figueras-Aloy J, Rodriguez-Miguelez JM, Iriondo-Sanz M, Salvia-Roiges MD, Botet-Mussons F, Carbonell-Estrany X. Intravenous immunoglobulin and necrotizing enterocolitis in newborns with hemolytic disease. Pediatrics. 2010 Jan. 125(1):139-44. [QxMD MEDLINE Link].

54. Maisels MJ, Yang H. Tin-mesoporphyrin in the treatment of refractory hyperbilirubinemia due to Rh incompatibility. J Perinatol. 2012 Nov. 32(11):899-900. [QxMD MEDLINE Link].

55. Vaughan JI, Warwick R, Letsky E, Nicolini U, Rodeck CH, Fisk NM. Erythropoietic suppression in fetal anemia because of Kell alloimmunization. Am J Obstet Gynecol. 1994 Jul. 171(1):247-52. [QxMD MEDLINE Link].

56. Bowman J. The management of hemolytic disease in the fetus and newborn. Semin Perinatol. 1997 Feb. 21(1):39-44. [QxMD MEDLINE Link].

57. Moise KJ Jr, Argoti PS. Management and prevention of red cell alloimmunization in pregnancy: a systematic review. Obstet Gynecol. 2012 Nov. 120(5):1132-9. [QxMD MEDLINE Link].

58. Fasano RM. Hemolytic disease of the fetus and newborn in the molecular era. Semin Fetal Neonatal Med. 2016 Feb. 21 (1):28-34. [QxMD MEDLINE Link].

59. Zimmerman R, Carpenter RJ Jr, Durig P, Mari G. Longitudinal measurement of peak systolic velocity in the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a prospective multicentre trial with intention-to-treat. BJOG. 2002 Jul. 109(7):746-52. [QxMD MEDLINE Link].

60. ACOG Practice Bulletin No. 75: management of alloimmunization. Obstet Gynecol. 2006 Aug. 108(2):457-64. [QxMD MEDLINE Link].

61. Opekes D, seward G, Vandenbussche F, et al. Minimally invasive management of rh alloimmunization: Can amniotic fluid delta OD 450 be replaced by Doppler studies? A prospective study multicenter trial. Am J Obstet Gynecol. 2004. 191:S3.

62. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. 2008 Jul. 112(1):164-76. [QxMD MEDLINE Link].

63. Scheier M, Hernandez-Andrade E, Fonseca EB, Nicolaides KH. Prediction of severe fetal anemia in red blood cell alloimmunization after previous intrauterine transfusions. Am J Obstet Gynecol. 2006 Dec. 195(6):1550-6. [QxMD MEDLINE Link].

64. Detti L, Oz U, Guney I, Ferguson JE, Bahado-Singh RO, Mari G. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol. 2001 Nov. 185(5):1048-51. [QxMD MEDLINE Link].

65. Schumacher B, Moise KJ. Fetal transfusion for red blood cell alloimmunization in pregnancy. Obstet Gynecol. 1996 Jul. 88(1):137-50. [QxMD MEDLINE Link].

66. Trevett TN, Dorman K, Lamvu G, Moise KJ. Antenatal maternal administration of phenobarbital for the prevention of exchange transfusion in neonates with hemolytic disease of the fetus and newborn. Am J Obstet Gynecol. 2005 Feb. 192(2):478-82. [QxMD MEDLINE Link].

67. Moise KJ. Grand Rounds: Rh disease: It's still a threat. Contemporary Ob/Gyn. 2004/05. 49:34-48.

68. Nwogu LC, Moise KJ Jr, Klein KL, Tint H, Castillo B, Bai Y. Successful management of severe red blood cell alloimmunization in pregnancy with a combination of therapeutic plasma exchange, intravenous immune globulin, and intrauterine transfusion. Transfusion. 2017 Dec 17. [QxMD MEDLINE Link].

69. Voto LS, Mathet ER, Zapaterio JL, Orti J, Lede RL, Margulies M. High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease. J Perinat Med. 1997. 25(1):85-8. [QxMD MEDLINE Link].

70. Kriplani A, Singh BM, Mandal K. Fetal intravenous immunoglobulin therapy in Rhesus Hemolytic Disease. Gynecol Obstet Invest. 2007. 63:176-180.

71. Matsuda H, Yoshida M, Wakamatsu H, Furuya K. Fetal intraperitoneal injection of immunoglobulin diminishes alloimmune hemolysis. J Perinatol. 2011 Apr. 31(4):289-92. [QxMD MEDLINE Link].

72. Moise KJ. Fetal anemia due to non-Rhesus-D red-cell alloimmunization. Semin Fetal Neonatal Med. 2008 Aug. 13(4):207-14. [QxMD MEDLINE Link].

73. Gottstein R, Cooke RW. Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed. 2003 Jan;88(1):F6-10. 88(1). 2003:F6-10. [QxMD MEDLINE Link].

74. Kappas A. A method for interdicting the development of severe jaundice in newborns by inhibiting the production of bilirubin. Pediatrics. 2004 Jan. 113(1 Pt 1):119-23. [QxMD MEDLINE Link].

75. Ovali F, Samanci N, Dagoglu T. Management of late anemia in Rhesus hemolytic disease: use of recombinant human erythropoietin (a pilot study). Pediatr Res. 1996 May. 39(5):831-4. [QxMD MEDLINE Link].

76. Steiner LA, Bizzarro MJ, Ehrenkranz RA, Gallagher PG. A decline in the frequency of neonatal exchange transfusions and its effect on exchange-related morbidity and mortality. Pediatrics. 2007 Jul. 120(1):27-32. [QxMD MEDLINE Link].

77. Smits-Wintjens VE, Walther FJ, Rath ME, Lindenburg IT, te Pas AB, Kramer CM. Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial. Pediatrics. 2011 Apr. 127(4):680-6. [QxMD MEDLINE Link].

78. Stasi R. Rozrolimupab, symphobodies against rhesus D, for the potential prevention of hemolytic disease of the newborn and the treatment of idiopathic thrombocytopenic purpura. Curr Opin Mol Ther. 2010 Dec. 12(6):734-40. [QxMD MEDLINE Link].

79. Watchko JF. Common hematologic problems in the newborn nursery. Pediatr Clin North Am. 2015 Apr. 62 (2):509-24. [QxMD MEDLINE Link].

80. Toly-Ndour C, Mourtada H, Huguet-Jacquot S, et al. Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer in the management of high-titer anti-D maternal alloimmunization. Transfusion. 2017 Nov 29. [QxMD MEDLINE Link].

81. Stetson B, Scrape S, Markham KB. Anti-M alloimmunization: management and outcome at a single institution. AJP Rep. 2017 Oct. 7 (4):e205-10. [QxMD MEDLINE Link]. [Full Text].

Sameer Wagle, MBBS, MD Consulting Staff, Division of Neonatology, Northwest Medical Center of Springdale and Willow Creek Women’s Hospital

Sameer Wagle, MBBS, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Prashant G Deshpande, MD Attending Pediatrician, Department of Pediatrics, Christ Hospital Medical Center and Hope Children's Hospital; Assistant Clinical Professor of Pediatrics, Midwestern University

Prashant G Deshpande, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Telemedicine Association

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David A Clark, MD Professor and Martha Lepow Chairman of Pediatrics, Professor of Obstetrics and Gynecology, Albany Medical College; Director, Children's Hospital at Albany Medical Center

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Forestry Association, American Pediatric Society, Capital District Pediatric Society, Christian Medical and Dental Associations, European Society for Paediatric Research, Eastern Society for Pediatric Research, Floyd W Denny Pediatric Alumni Society, Medical Society of the State of New York, New York Academy of Sciences, Society for Pediatric Research

Disclosure: Nothing to disclose.

Muhammad Aslam, MD Professor of Pediatrics, University of California, Irvine, School of Medicine; Neonatologist, Division of Newborn Medicine, Department of Pediatrics, UC Irvine Medical Center

Muhammad Aslam, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

• Print this section
• Print the entire contents of
• Print the entire contents of article