Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 17 , ISSUE 3 ( July-September, 2023 ) > List of Articles

REVIEW ARTICLE

Diagnosis and Treatment of Fetus Anemia: Current Status

Liliana S Voto, Norberto D Margulies

Keywords : Fetal Anemia, Fetal-neonatal morbidity, Mortality

Citation Information : Voto LS, Margulies ND. Diagnosis and Treatment of Fetus Anemia: Current Status. Donald School J Ultrasound Obstet Gynecol 2023; 17 (3):223-233.

DOI: 10.5005/jp-journals-10009-1986

License: CC BY-NC 4.0

Published Online: 30-09-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Fetal anemia is defined as the diminished concentration of fetal hemoglobin below two standard deviations for gestational age. In Argentina as well as in most developing countries, this disease is one of the leading causes of fetal-neonatal morbidity and mortality (5% of perinatal deaths) due to the lack of appropriate prophylaxis with postpartum anti-D γ-globulin and inadequate prenatal control. Fetal anemia is originated in the mother due to the presence of specific antibodies–originated In Rhesus factor (Rh)—negative mothers whose husbands are Rh-positive and whose immunization occurred during pregnancy, abortion, postpartum or incompatible transfusions that pass through the placenta agglutinate and hemolyze fetal red blood cells, thus causing fetal anemia and hemolytic disease. In the most severe cases, the fetus can be hydropic or die in utero due to congestive cardiac failure. In our experience, the immunization frequency in Rh-negative patients during their second pregnancy with compatible Rh-positive fetuses is 12–15%. The cornerstone of the follow-up of the sensitized Rh-negative woman is a composite of an appropriate anamnesis, the indirect Coombs test, titration of anti-D antibodies, ultrasound (US) middle cerebral artery (MCA) peak systolic velocity, amniotic fluid spectrophotometry, amniocentesis/cordocentesis, and antenatal fetal monitoring. The pillar of the treatment of severe maternal-fetal Rh-incompatibility to prevent fetal death and allow the fetus to reach viability is intrauterine fetal transfusion (by the intraperitoneal route or intravascular fetal transfusion), high intravenous dose immunoglobulin (HDIVIg) as a single treatment or followed by intrauterine transfusions (IUTs). The neonatal treatment of the newborn is based on phototherapy and HDIVIg, which reduce the frequency of neonatal transfusions needed and the bilirubin maximum levels.


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  1. Margulies M, Voto LS, Mathet E, et al. High-dose intravenous IgG for the treatment of severe rhesus alloimmunization. Vox Sang 1991;61(3):181–189. DOI: 10.1111/j.1423-0410.1991.tb00944.x
  2. Diamond LK, Blackfan KD, Batty JM. Erythroblastosis fetalis and its association with universal edema of the fetus, icterus gravis neonatorum, and anemia of the newborn. J Pediatr 1932;1(3):269–309. DOI: 10.1016/S0022-3476(32)80057-0
  3. Darrow RR. Icterus gravis (erythroblastosis neonatorum) examination of etiologic considerations. Arch Pathol 1938;25:378–417.
  4. Landsteiner K, Wiener AS. An agglutinable factor in human blood recognized by immune sera for Rhesus blood. Proc Soc Exp Biol Med 1940;43(1):223. DOI: 10.3181/00379727-43-11151
  5. Levine P. The role of isoimmunization in transfusion accidents in pregnancy and erythroblastosis fetalis. Am J Obstet Gynecol 1941;42:165. DOI: 10.1093/ajcp/11.12.898
  6. Wallerstein H. The treatment of erythroblastosis fetalis by substitution transfusion. Blood 1948;3(2):170–179. DOI: 10.1182/blood.v3.special_issue_number_2.170.170
  7. Allen FH, Diamond LK, Vaughan JC. Eryhtroblastosis fetalis: VI. Prevention of kernicterus. Am J Dis Child 1950;80(5):779–791. PMID: 14777158.
  8. Allen FH Jr. Induction of labor in the management of erythroblastosis fetalis. Quatr Rev Pediat 1950;12:1–5. DOI: 10.1097/00006254-195708000-00023
  9. Chown B, Bowman WD. The place of early delivery in the prevention of foetal death from erythroblastosis. Pediatr Clin North Am 1958;279–285. DOI: 10.1016/s0031-3955(16)30649-6
  10. Cremer RJ, Perryman PW, Richards DH. Influence of light on the hyperbilirubinaemia of infants. Lancet 1958;1(7030):1094–1097. DOI: 10.1016/s0140-6736(58)91849-x
  11. Bevis DC. The antenatal prediction of haemolytic disease of the newborn. Lancet 1952;1(6704):395–398. DOI: 10.1016/s0140-6736(52)90006-8
  12. Liley AW. Liquor amnil analysis in the management of the pregnancy complicated by resus sensitization. Am J Obstet Gynecol 1961;82:1359–1370. DOI: 10.1016/s0002-9378(16)36265-2
  13. Liley AW. Intrauterine transfusion of foetus in haemolytic disease. Br Med J 1963;2(5365):1107–1109. DOI: 10.1136/bmj.2.5365.1107
  14. Freda VJ, Gorman JG, Pollack W. Successful prevention of experimental rh sensitization in man with an anti-rh gamma2-globulin antibody preparation: a preliminary report. Transfusion 1964;4:26–32. DOI: 10.1111/j.1537-2995.1964.tb02824.x
  15. Hohlfeld P, Wirthner D, Tissot JA. Perinatal hemolytic disease: physiopathology. J Gynecol Obstet Biol Reprod 1998;27(2):135–43.
  16. Palfi M, Hildén JO, Gottvall T, et al. Placental transport of maternal immunoglobulin G in pregnancies at risk of Rh (D) hemolytic disease of the newborn. Am J Reprod Immunol 1998;39(5):323–328. DOI: 10.1111/j.1600-0897.1998.tb00525.x
  17. Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000;342(1):9–14. DOI: 10.1056/NEJM200001063420102
  18. Zimmerman R, Carpenter RJ Jr, 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 2002;109(7):746–752. DOI: 10.1111/j.1471-0528.2002.01314.x
  19. Nishie EN, Brizot ML, Liao AW, et al. A comparison between middle cerebral artery peak systolic velocity and amniotic fluid optical density at 450 nm in the prediction of fetal anemia. Am J Obstet Gynecol 2003;188(1):214–219. DOI: 10.1067/mob.2003.63
  20. Liley AW. Errors in the assessment of hemolytic disease from amniotic fluid. Am J Obstet Gynecol 1963;86:485–494. DOI: 10.1016/0002-9378(63)90174-1
  21. In: The perinatal medicine of the new millennium: proceedings of the 5th World Congress of Perinatal Medicine 2001;23–27.
  22. Klumper FJ, van Kamp IL, Vandenbussche FP, et al. Benefits and risks of fetal red-cell transfusion after 32 weeks gestation. Eur J Obstet Gynecol Reprod Biol 2000;92(1):91–96. DOI: 10.1016/s0301-2115(00)00430-9
  23. Dodd JM, Andersen C, Dickinson JE, et al. Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell alloimmunization: a randomized trial. Ultrasound Obstet Gynecol 2018;51(3):306–312. DOI: 10.1002/uog.18807
  24. 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):85–88. DOI: 10.1515/jpme.1997.25.1.85
  25. Porter TF, Silver RM, Jackson GM, et al. Intravenous immune globulin in the management of severe Rh D hemolytic disease. Obstet Gynecol Surv 1997;52(3):193–197. DOI: 10.1097/00006254-199703000-00022
  26. Voto LS, Sexer H, Ferreiro G, et al. Neonatal administration of high-dose intravenous immunoglobulin in rhesus hemolytic disease. J Perinat Med 1995;23(6):443–451. DOI: 10.1515/jpme.1995.23.6.443
  27. Mukhopadhyay K, Murki S, Narang A, et al. Intravenous immunoglobulins in rhesus hemolytic disease. Indian J Pediatr 2003;70(9):697–699. DOI: 10.1007/BF02724308
  28. Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2002;100(3):600–611. DOI: 10.1016/s0029-7844(02)02180-4
  29. Harkness UF, Spinnato JA. Prevention and management of RhD isoimmunization. Clin Perinatol 2004;31(4):721–742, vi. DOI: 10.1016/j.clp.2004.06.005
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