Hemolytic Disease of Newborn Medication

  • Author: Sameer Wagle, MBBS, MD; Chief Editor: Ted Rosenkrantz, MD   more...
 
Updated: May 18, 2011
 

Immunomodulators

Class Summary

These agents normalize antibody levels in patients with primary defective antibody synthesis. They prevent and treat certain bacterial and viral infections and reduce the immune-mediated hemolysis and phagocytosis.

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Intravenous immunoglobulin (Gamimune, Gammagard, Sandoglobulin, Gammar-P)

 

Several studies have reported success in minimizing the need for exchange transfusion in severe HDN with IVIG. Effective adjunct to phototherapy. Mechanism of action appears to be related to blockage of Fc receptors in the neonatal reticuloendothelial system. Studies have also documented decreased hemolysis after administration of IVIG using carboxyhemoglobin levels. Administration in doses of 500-1000 mg/kg in the first few hours of life to a newborn with severe hemolysis should be considered. However, efficacy depends on timing of administration, duration of treatment, and severity of hemolysis. Should be prepared by and dispensed from pharmacy and should not be mixed with normal saline. Dispensed as either 3% or 6% solution.

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Colony-stimulating Factor

Class Summary

These agents may be required to correct anemia.

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Epoetin alfa, recombinant (Epogen, Procrit)

 

Purified glycoprotein produced from mammalian cells modified with gene coding for human erythropoietin (EPO). Amino acid sequence is identical to that of endogenous EPO. Biological activity mimics human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces release of reticulocytes from bone marrow into the blood stream.

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Competitive heme oxygenase inhibitor

Class Summary

Phase III clinical trials have been completed in the United States on stannsoporfin, a competitive heme oxygenase inhibitor. The drug is currently available via a compassionate use protocol.

Stannsoporfin (SnMP, Stanate)

 

Also known as tin-mesoporphyrin. Investigational in the United States. Phase III clinical trials completed. Structural analog of heme that blocks heme oxygenase (HO-1), a rate-limiting enzyme in bilirubin production, thereby preventing the conversion of heme to bilirubin. Heme is excreted unchanged in bile and is not stored in tissue. It is inert and does not enter the brain or interact with DNA. It does not affect previously formed bilirubin conjugation or excretion in liver. Several randomized, controlled and, when possible, blinded studies over the last decade that involved >700 neonates with all principle forms of neonatal jaundice have shown SnMP to be effective in preventing and blocking jaundice progression. Phototherapy was eliminated in 97% of treated infants.

Also inhibits nitric oxide synthase and soluble guanylyl cyclase. Repeated doses lead to inhibition of intestinal heme oxygenase involved in iron absorption and may lead to anemia. It also stimulates HO-1 transcription and protein levels. The half-life as measured in healthy adult volunteers is 3.8 h.

Available under the rules of a compassionate use protocol by WellSpring Pharmaceutical and InfaCare Pharmaceutical Corporations. For details, contact Dr Benjamin Levinson (732) 938-5885 ext 224, or by email at blevin@wellsringpharm.com.

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Contributor Information and Disclosures
Author

Sameer Wagle, MBBS, MD  Consulting Staff, Division of Neonatology, Northwest Medical Center of Washington County

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

Disclosure: Nothing to disclose.

Coauthor(s)

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

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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 College of Nutrition, American College of Physician Executives, and American Heart 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  Chairman, Professor, Department of Pediatrics, Albany Medical College

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical & Dental Society, Medical Society of the State of New York, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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.

References

  1. Bowman JM. Hemolytic disease (erythroblastosis fetalis). In: 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. Van der Schoot CE, Tax GH, Rijnders RJ, et al. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed. Transfus Med Rev. Jan 2003;17(1):31-44. [Medline].

  4. Singleton BK, Green CA, Avent ND, Martin PG, Smart E, Daka A. 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. Jan 1 2000;95(1):12-8. [Medline].

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

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

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

  8. Martin JA, Hamilton BE, Sutton PD et al. Births; final data for 2002. Natl Vital Stat Rep. 2002;52:1-116.

  9. Eder AF. Update on HDFN: new information on long-standing controversies. Immunohematol. 2006;22(4):188-95. [Medline].

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

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

  12. Harkness UF, Spinnato JA. Prevention and management of RhD isoimmunization. Clin Perinatol. Dec 2004;31(4):721-42, vi. [Medline].

  13. 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. [Medline].

  14. 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. [Medline].

  15. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. Jul 2008;112(1):164-76. [Medline].

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

  17. Bowman JM, Pollock JM. Amniotic fluid spectrophotometry and early delivery in the management of erythroblastosis fetalis. Pediatr. May 1965;35:815-835. [Medline].

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

  19. 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. May 1993;168(5):1370-6. [Medline].

  20. 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. [Medline].

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

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

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

  24. Christensen RD, Henry E. Hereditary spherocytosis in neonates with hyperbilirubinemia. Pediatrics. Jan 2010;125(1):120-5. [Medline].

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

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

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

  28. 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. Dec 2009;98(12):1896-901. [Medline].

  29. Vaughan JI, Warwick R, Letsky E, et al. Erythropoietic suppression in fetal anemia because of Kell alloimmunization. Am J Obstet Gynecol. Jul 1994;171(1):247-52. [Medline].

  30. Bowman J. The management of hemolytic disease in the fetus and newborn. Semin Perinatol. Feb 1997;21(1):39-44. [Medline].

  31. Segata M, Mari G. Fetal anemia: new technologies. Curr Opin Obstet Gynecol. Apr 2004;16(2):153-8. [Medline].

  32. Zimmerman R, Carpenter RJ, Durig P, et al. 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. Jul 2002;109(7):746-52. [Medline].

  33. ACOG Practice Bulletin No. 75: management of alloimmunization. Obstet Gynecol. Aug 2006;108(2):457-64. [Medline].

  34. 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.

  35. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. Jul 2008;112(1):164-76. [Medline].

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

  37. 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. Feb 2005;192(2):478-82. [Medline].

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

  39. Voto LS, Mathet ER, Zapaterio JL, et al. 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. [Medline].

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

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

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

  43. 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. [Medline].

  44. 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. Apr 2011;170(4):461-7. [Medline].

  45. Smits-Wintjens VE, Walther FJ, Rath ME, Lindenburg IT, Te Pas AB, Kramer CM, et al. Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial. Pediatrics. Apr 2011;127(4):680-6. [Medline].

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

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

  48. [Guideline] Maisels MJ, Baltz RD, Bhutani V, et al. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. Jul 2004;114(1):297-316. [Medline].

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

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

  51. Peterec SM. Management of neonatal Rh disease. Clin Perinatol. Sep 1995;22(3):561-92. [Medline].

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

  53. Figueras-Aloy J, Rodriguez-Miguelez JM, Iriondo-Sanz M, et al. Intravenous immunoglobulin and necrotizing enterocolitis in newborns with hemolytic disease. Pediatrics. Jan 2010;125(1):139-44. [Medline].

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

  55. 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. Jul 2007;120(1):27-32. [Medline].

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

 
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Liley curve. This graph illustrates an example of amniotic fluid spectrophotometric reading of 0.206, which when plotted at 35 weeks' gestation falls into zone 3, indicating severe hemolytic disease.
Modified Liley curve for gestation of less than 24 weeks showing that bilirubin levels in amniotic fluid peak at 23-24 weeks' gestation.
Queenan Curve: Modified Liley curve that shows delta-OD 450 values at 14-40 weeks' gestation.
Slopes for peak systolic velocity in middle cerebral artery (MCA) for normal fetuses (dotted line), mildly anemic fetuses (thin line), and severely anemia fetuses (thick line).
Management of first affected pregnancy.
Management of pregnant women with previously affected fetus.
Table. Comparison of Rh and ABO Incompatibility
CharacteristicsRhABO
Clinical aspectsFirst born5%50%
Later pregnanciesMore severeNo increased severity
Stillborn/hydropsFrequentRare
Severe anemiaFrequentRare
JaundiceModerate to severe, frequentMild
Late anemiaFrequentRare
Laboratory findingsDirect antibody testPositiveWeakly positive
Indirect Coombs testPositiveUsually positive
SpherocytosisRareFrequent
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