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Chapter 6 - Red cell alloimmunization

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

By
Janet Brennand  and
Alan Cameron
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
Mark D. Kilby
Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson
Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes
Affiliation:
Department of Obstetrics, Leiden University Medical Center
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Summary

Introduction

Red cell alloimmunization, with its resultant fetal anemia, continues to be a cause of perinatal morbidity and mortality. Recent decades have seen major advances in the understanding and management of the condition and it is the aim of this chapter to review this. In particular, the role of direct fetal therapy for fetal anemia will be described, which has been one of the success stories of fetal medicine.

Red cell alloimmunization in pregnancy

There is a risk of red cell alloimmunization in any pregnancy where the mother is exposed to fetal red cells that possess antigens for which her own red cells are negative. The underlying mechanism for this exposure during pregnancy is fetomaternal hemorrhage (FMH). As a result, the mother mounts an immune response that is initially composed of IgM antibodies – large molecules that do not cross the placenta. Later, IgG antibodies are produced that are able to cross the placenta. This represents the primary immune response. A second exposure to the foreign antigens, for example in the next pregnancy, results in the secondary immune response and a rapid production of IgG antibodies which cross the placenta and cause fetal red cell hemolysis. The risk and severity of alloimmunization increases with each subsequent pregnancy that is positive for the relevant red cell antigen.

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 55 - 66
Publisher: Cambridge University Press
Print publication year: 2012

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References

Moise, KJ Jr. Red blood cell alloimmunization in pregnancy. Semin Hematol 2005;42:169–78.Google Scholar
Van Kamp, IL, Klumper, FJCM, Oepkes, D, et al. Complications of intrauterine intravascular transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet Gynecol 2005;192:171–7.Google Scholar
Zipursky, A, Israels, LG. The pathogenesis and prevention of Rh immunization. Can Med Assoc J 1967;97:1245–57.Google Scholar
MacKenzie, IZ, Bowell, P, Gregory, H, et al. Routine antenatal rhesus D immunoglobulin prophylaxis: the results of a prospective 10 year study. Br J Obstet Gynaecol 1999;106:492–7.Google Scholar
Urbaniak, SJ. The scientific basis of antenatal prophylaxis. Br J Obstet Gynaecol 1998;105:11–18.Google Scholar
Crowther, CA, Keirse, MJ. Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev 2000;2:CD 000020.Google Scholar
National Institute for Clinical Excellence. Technology Appraisal No. 41. Guidance on the use of Routine Antenatal anti-D Prophylaxis for RhD-negative Women. London, NICE, 2002.
Ness, PM, Baldwin, ML, Niebyl, JR. Clinical high-risk designation does not predict excess fetal-maternal haemorrhage. Am J Obstet Gynecol 1987;156:154–8.Google Scholar
Bowman, JM, Pollock, JM, Penston E. Fetomaternal transplacental haemorrhage during pregnancy and after delivery. Vox Sang 1986;51:117–21.Google Scholar
Mayne, S, Parker, JH, Harden, TA, et al. Rate of RhD sensitisation before and after implementation of a community based antenatal prophylaxis programme. BMJ 1997;315:1588.Google Scholar
Flegel, WA. The genetics of the Rhesus blood group system. Blood Transfus 2007;5:50–7.Google Scholar
Moise, KJ Jr, Scumacher, B. Anaemia. In: Fisk, NM and Moise, KJ Jr. (eds.) Fetal Therapy, 1st edn. Cambridge University Press. 1997; 141–63.
Lo, YMD, Corbetta, N, Chamberlain, PF, et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:485–7.Google Scholar
Geifman-Holzman, O, Groegut, CA, Gaughan, JP. Diagnostic accuracy of non invasive fetal Rh genotyping from maternal blood – a meta-analysis. Am J Obstet Gynecol 2006;195:1163–73.Google Scholar
Finning, KM, Martin, P, Summers, J, et al. Fetal genotyping for the K (Kell) and Rh C, c, and E blood groups on cell-free fetal DNA in maternal plasma. Transfusion 2007;47:2126–33.Google Scholar
Wright, C. Cell-free Fetal Nucleic Acids for Non-invasive Prenatal Diagnosis. Report of the UK Expert Working Group. London, PHG Foundation, 2009.
Joint Working Group of the British Blood Transfusion Society and the RCOG. Recommendations for the use of anti-D immunoglobulin for Rh prophylaxis. Transfus Med 1999;9:93–7.Google Scholar
Gooch, A, Parker, J, Wray, J, Qureshi, H. Guideline for Blood Grouping and Antibody Testing in Pregnancy. London, British Committee for Standards in Haematology (BCSH), 2006.
Nicolaides, KH, Rodeck, CH. Maternal serum anti-D antibody concentration and assessment of rhesus isoimmunisation. BMJ 1992;304:1155–6.Google Scholar
Liley, AW. Liquor amnii analysis in the management of pregnancy complicated by rhesus sensitization. Am J Obstet Gynecol 1961;82:1359–70.Google Scholar
Nicolaides, KH, Rodeck, CH, Mibasham, RS, Kemp, JR. Have Liley charts outlived their usefulness? Am J Obstet Gynecol 1986;155:90–4.Google Scholar
Queenan, JT, Tomai, TP, Ural, SH, King, JC. Deviation in amniotic fluid optical density at a wavelength of 450nm in Rh-immunized pregnancies from 14 to 40 weeks’ gestation: a proposal for clinical management. Am J Obstet Gynecol 1993;168:1370–6.Google Scholar
Spinnato, JA, Clark, AL, Ralston, KK, et al. Hemolytic disease of the fetus: a comparison of the Queenan and extended Liley methods. Obstet Gynecol 1998;92:441–5.Google Scholar
Whitfield, CR, Neely, RA, Telford, ME. Amniotic fluid analysis in rhesus isoimmunisation. J Obstet Gynaecol Brit Cwlth 1968;75:121–7.Google Scholar
Bowman, JM. The management of Rh-isoimmunization. Obstet Gynecol 1978;52:1–16.Google Scholar
Tabor, A, Philip, J, Madsen, M, et al. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women. Lancet 1986;i(8493):1287–93.Google Scholar
Bowman, JM, Pollock, JM. Transplacental fetal hemorrhage after amniocentesis. Obstet Gynecol 1985;66:749–54.Google Scholar
Tabor, A, Bang, J, Norgaard-Pedersen, B. Feto-maternal haemorrhage with genetic amniocentesis: results of a randomized trial. Br J Obstet Gynaecol 1987;94:528–34.Google Scholar
Moise, KJ. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2002;100:600–11.Google Scholar
Whitecar, PW, Moise, KJ Jr. Sonographic methods to detect fetal anemia in red blood cell alloimmunization. Obstet Gynecol Surv 2000;55:240–50.Google Scholar
Vintzileos, AM, Campbell, WA, Storlazzi, E, et al. Fetal liver ultrasound measurements in isoimmunized pregnancies. Obstet Gynecol 1986;68:162–7.Google Scholar
Oepkes, D, Meerman, RH, Vandenbussche, FP, et al. Ultrasonographic fetal spleen measurements in red blood cell-alloimmunized pregnancies. Am J Obstet Gynecol 1983;169:121–8.Google Scholar
Oepkes, D. Invasive versus non-invasive testing in red-cell alloimmunized pregnancies. Eur J Obstet Gynecol Reprod Biol 2000;92:83–9.Google Scholar
Dukler, D, Oepkes, D, Seaward, G, et al. Noninvasive tests to predict fetal anemia: a study comparing Doppler and ultrasound parameters. Am J Obstet Gynecol 2003;188:1310–14.Google Scholar
Fan, FC, Chen, RYZ, Schuessler, GB, Chien, S. Effects of hematocrit variations on regional hemodynamics and oxygen transport in the dog. Am J Physiol 1984; 238:H545–52.Google Scholar
Fumia, FD, Edelstone, DI, Holzman, IR. Blood flow and oxygen delivery to fetal organs as functions of fetal hematocrit. Am J Obstet Gynecol 1984;150:274–82.Google Scholar
Giles, WB, Trudinger, BJ. Umbilical cord whole blood viscosity and the umbilical artery flow velocity time waveforms: a correlation. Br J Obstet Gynaecol 1986;93:466–70.Google Scholar
Gill, RW. Measurement of blood flow by ultrasound: accuracy and sources of error. Ultrasound Med Biol 1985;11:625–40.Google Scholar
Mari, G, Andrignolo, A, Abuhamad, AZ, et al. Diagnosis of fetal anemia with Doppler ultrasound in the pregnancy complicated by maternal blood group immunization. Ultrasound Obstet Gynecol 1995;5:400–5.Google Scholar
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;342:9–14.Google Scholar
Nicolaides, KH, Fontanarosa, M, Gabbe, SG, Rodeck, CH. Failure of ultrasonographic parameters to predict the severity of fetal anemia in rhesus isoimmunization. Am J Obstet Gynecol 1988;158:920–6.Google Scholar
Mari, G, Detti, L, Oz, U, et al. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol 2002;99:589–93.Google Scholar
Detti, L, Mari, G, Akiyama, M, et al. Longitudinal assessment of the middle cerebral artery peak systolic velocity in healthy fetuses and in fetuses at risk for anemia. Am J Obstet Gynecol 2002;187:937–9.Google Scholar
Nicolaides, KH, Soothill, PW, Rodeck, CH, Clewell, W. Rh Disease: intravascular fetal blood transfusion by cordocentesis. Fetal Ther 1986;1:185–92.Google Scholar
Welch, R, Rampling, MW, Anwar, A, et al. Changes in hemorheology with fetal intravascular transfusion. Am J Obstet Gynecol 1994;170:726–32.Google Scholar
Mari, G, Rahman, F, Olofsson, P, et al. Increase of fetal hematocrit decreases the middle cerebral artery peak systolic velocity in pregnancies complicated by rhesus alloimmunization. J Matern Fetal Med 1997;6:206–8.Google Scholar
Detti, L, Oz, U, Guney, I, et al. Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization. Am J Obstet Gynecol 2001;185:1048–51.Google Scholar
Deren, O, Onderoglu, L. The value of middle cerebral artery systolic velocity for initial and subsequent management in fetal anemia. Eur J Obstet Gynecol Reprod Biol 2002;101:26–30.Google Scholar
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;195:1550–6.Google Scholar
Mari, G, Zimmermann, R, Moise, KJ, Deter, RL. Correlation between middle cerebral artery peak systolic velocity and fetal hemoglobin after 2 previous intrauterine transfusions. Am J Obstet Gynecol 2005;193:1117–20.Google Scholar
Delle Chiaie, L, Buck, G, Grab, D, Terinde, R. Prediction of fetal anemia with doppler measurement of the middle cerebral artery peak systolic velocity in pregnancies complicated by maternal blood group alloimmunization or parvovirus B19 infection. Ultrasound Obstet Gynecol 2001;18:232–6.Google Scholar
Cosmi, E, Mari, G, Delle Chiaie, L, et al. Noninvasive diagnosis by doppler ultrasonography of fetal anemia resulting from parvovirus infection. Am J Obstet Gynecol 2002;187:1290–3.Google Scholar
Van Dongen, H, Klumper, FJCM, Sikkel, E, et al. Non-invasive tests to predict fetal anemia in Kell-alloimmunized pregnancies. Ultrasound Obstet Gynecol 2005;25:341–5.Google Scholar
Sueters, M, Arabin, B, Oepkes, D. Doppler sonography for predicting fetal anemia caused by massive fetomaternal hemorrhage. Ultrasound Obstet Gynecol 2003;22:186–9.Google Scholar
Senat, MV, Loizeau, S, Couderc, S, et al. The value of middle cerebral artery peak systolic velocity in the diagnosis of fetal anemia after intrauterine death of one monochorionic twin. Am J Obstet Gynecol 2003;189:1320–4.Google Scholar
Haak, MC, Oosterhof, H, Mouw, RJ, et al. Pathophysiology and treatment of fetal anemia due to placental chorioangioma. Ultrasound Obstet Gynecol 1999;14:68–70.Google Scholar
Leung, WC, Oepkes, D, Seaward, G, Ryan, G. Serial sonographic findings of four fetuses with homozygous alpha-thalassemia-1 from 21 weeks onwards. Ultrasound Obstet Gynecol 2002;19:56–9.Google Scholar
Oepkes, D, Seaward, G, Vandenbussche, FPHA, et al. Doppler ultrasonography versus amniocentesis to predict fetal anemia. N Engl J Med 2006;355:156–64.Google Scholar
Liley, AW. Intrauterine transfusion of foetus in haemolytic disease. Br Med J 1963;2:1107–9.Google Scholar
Fox, C, Martin, W, Somerset, DA, et al. Early intraperitoneal transfusion and adjuvant maternal immunoglobulin therapy in the treatment of severe red cell alloimmunisation, prior to fetal intravascular transfusion. Fetal Diagn Ther 2008;23(2):159–63.Google Scholar
Cooperberg, PL, Carpenter, CW. Ultrasound as an aid in intrauterine transfusion. Am J Obstet Gynecol 1977;128:239–41.Google Scholar
Rodeck, CH, Kemp, JR, Holman, CA, et al. Direct intravascular fetal blood transfusion by fetoscopy in severe rhesus isoimmunisation. Lancet 1981;i:625–7.Google Scholar
Westgren, M, Selbing, A, Stangenberg, M. Fetal intracardiac transfusions in patients with severe rhesus isoimmunisation. BMJ 1988;296:885–6.Google Scholar
Schumacher, B, Moise, KJ. Fetal transfusion for red blood cell alloimmunization in pregnancy. Obstet Gynecol 1996;88:137–50.Google Scholar
MacGregor, SN, Socol, ML, Pielet, BW, et al. Prediction of hematocrit decline after intravascular transfusion. Am J Obstet Gynecol 1989;161:1491–3.Google Scholar
Jones, HM, Lynch, DC, Nicolaides, K, Rodeck, CH. Survival of transfused adult cells in the fetus. Fetal Ther 1986;1:193–5.Google Scholar
Weiner, CP, Wenstrom, KD, Sipes, SL, Williamson, RA. Risk factors for cordocentesis and fetal intravascular transfusion. Am J Obstet Gynecol 1991;165:1020–5.Google Scholar
Poissonnier, MH, Brossard, Y, Demedeiros, N, et al. Two hundred intrauterine exchange transfusions in severe blood incompatibilities. Am J Obstet Gynecol 1989;161:709–13.Google Scholar
Vietor, HE, Kanhai, HH, Brand, A. Induction of additional red cell alloantibodies after intrauterine transfusions. Transfusion 1994;34:970–4.Google Scholar
Schonewille, H, Klumper, FJ, van de Watering, LM, et al. High additional maternal red cell alloimmunization after Rhesus- and K-matched intrauterine intravascular transfusion for hemolytic disease of the fetus. Am J Obstet Gynecol 2007;196:143–6.Google Scholar
Somerset, DA, Moore, A, Whittle, MJ, et al. An audit of outcome in intravascular transfusions using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis. Fetal Diagn Ther 2006;21:272–6.Google Scholar
Van Kamp, IL, Klumper, FCJM, Bakkum, RSLA, et al. The severity of immune fetal hydrops is predictive of fetal outcome after intrauterine treatment. Am J Obstet Gynecol 2001;185:668–73.Google Scholar
Binks, AS, Lind, T, McNay, RA. Effects of rhesus haemolytic disease upon birthweight. J Obstet Gynaecol Brit Cwlth 1973;80:301–4.Google Scholar
Roberts, A, Grannum, P, Belanger, K, et al. Fetal growth and birthweight in isoimmunized pregnancies after intravenous intrauterine transfusion. Fetal Diagn Ther 1993;8:407–11.Google Scholar
Janssens, HM, de Haan, MJ, van Kamp, IL, et al. Outcome for children treated with fetal intravascular transfusions because of severe blood group antagonism. J Pediatr 1997;131:373–80.Google Scholar
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;179:858–63.Google Scholar
Verduin, EP, Lindenburg, ITM, Smits-Wintjens, VEHJ et al. Long-Term follow up after inta-Uterine transfusionS; the LOTUS study. BMC Pregnancy Childbirth 2010;10:77.Google Scholar
Yinon, Y, Visser, J, Kelly, EN, et al. Early intrauterine transfusion in severe red blood cell alloimmunization. Ultrasound Obstet Gynecol 2010;36:601–6.Google Scholar
Poissonnier, MH, Picone, O, Brossard, Y, Lepercq, J. Intravenous fetal exchange transfusion before 22 weeks of gestation in early and severe red-cell fetomaternal alloimmunization. Fetal Diagn Ther 2003;18:467–71.Google Scholar
De la Camara, C, Arrieta, R, Gonszales, A, et al. High-dose intravenous immunoglobulin as the sole prenatal treatment for severe Rh immunization. N Engl J Med 1988;318:519–20.Google Scholar
Berlin, G, Selbing, A, Gottvall, T. Plasma exchange and intravenous immunoglobulin treatment of the mother to diminish fetal hemolytic disease. Transfus Sci 1990;11:85–90.Google Scholar
Margulies, M, Voto, LS, Mathet, E, et al. High-dose intravenous IgG for the treatment of severe Rhesus alloimmnization. Vox Sang 1991;61:181.Google Scholar
Caine, ME, Mueller-Heubach, E. Kell sensitzation in pregnancy. Am J Obstet Gynecol 1986;154:85–90.Google Scholar
Leggat, HM, Gibson, JM, Barron, SL, Reid, MM. Anti-Kell in pregnancy. Br J Obstet Gynaecol 1991;98:162–5.Google Scholar
Weiner, CP, Widness, JA. Decreased fetal erythropoiesis and hemolysis in Kell haemolytic anemia. Am J Obstet Gynecol 1996;174:547–51.Google Scholar
Weinstein, L. Irregular antibodies causing haemolytic disease of the newborn. Obstet Gynecol Surv 1976;31:581–91.Google Scholar
Bowman, JM, Pollock, JM, Manning, FA, et al. Maternal Kell blood group alloimmunization. Obstet Gynecol 1992;79:239–44.Google Scholar
McKenna, DS, Nagaraja, HN, O’Shaughnessy, R. Management of pregnancies complicated by anti-Kell isoimmunization. Obstet Gynecol 1999;93:667–73.Google Scholar
Grant, SR, Kilby, MD, Meer, L, et al. The outcome of pregnancy in Kell alloimmunisation. BJOG 2000;107:481–5.Google Scholar
Wenk, RE, Goldstein, P, Felix, JK. Kell alloimmunization, hemolytic disease of the newborn, and perinatal management. Obstet Gynecol 1985;66:473–6.Google Scholar
van Vamelen, DJ, Klumper, FJ, de Haas, M, et al. Obstetric history and antibody tier in estimating severity of Kell alloimmunization in pregnancy. Obstet Gynecol 2007;109:1093–8.Google Scholar
Enders, M, Weidner, A, Zoellner, I, et al. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn 2004;24:513–18.Google Scholar
Miller, E, Fairley, CK, Cohen, BJ, Seng, C. Immediate and long term outcome of human parvovirus B19 infection in pregnancy. Br J Obstet Gynaecol 1998;105:174–8.Google Scholar
Yaegashi, N, Niinuma, T, Chisaka, H, et al. The incidence of, and factors leading to, parvovirus B19-related hydrops fetalis following maternal infection; report of 10 cases and meta-analysis. J Infect 1998;37:28–35.Google Scholar
Fairley, CK, Smoleniec, JS, Caul, OE, Miller, E. Observational study of effect of intrauterine transfusions on outcome of fetal hydrops after parvovirus B19 infection. Lancet 1995;346:1335–7.Google Scholar
Rodis, JF, Rodner, C, Hansen, AA, et al. Long-term outcome of children following maternal human parvovirus B19 infection. Obstet Gynecol 1998;91:125–8.Google Scholar
Dembinski, J, Haverkamp, F, Maara, H, et al. Neurodevelopmental outcome after intrauterine red cell transfusion for parvovirus B19-induced fetal hydrops. BJOG 2002;109:1232–4.Google Scholar
Nagel, HTC, De Haan, TR, Vandenbusshe, FPHA, et al. Long-term outcome after fetal transfusion for hydrops associated with parvovirus B19 infection. Obstet Gynecol 2007;109:42–7.Google Scholar
Vichensky, EP. Alpha thalassemia major – new mutations, intrauterine management and outcomes. Haematology Am Soc Hematol Educ Program 2009:35–41.Google Scholar

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