Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 1 , Pages 10-20 , March 2006

Clinical Potential for Noninvasive Prenatal Diagnosis Through Detection of Fetal Cells in Maternal Blood

  • Yuditiya Purwosunu

      Affiliations

    • Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
    • ,
  • Akihiko Sekizawa

      Affiliations

    • Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
    • Corresponding Author InformationCorrespondence to: Dr. Akihiko Sekizawa, Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
    • ,
  • Keiko Koide

      Affiliations

    • Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
    • ,
  • Shiho Okazaki

      Affiliations

    • Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
    • ,
  • Antonio Farina

      Affiliations

    • Department of Histology and Embryology, Division of Prenatal Medicine, University of Bologna, Bologna, Italy
    • ,
  • Takashi Okai

      Affiliations

    • Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan

Received 6 February 2006 ,Revised 13 February 2006 ,Accepted 14 February 2006.

References 

  1. Schmorl G . Pathogisch-anatomische untersuchungen uber puerperaleklampsie . Leipzig: Vogel; 1893;
  2. Douglas GW , Thomas L , Carr M , Cullen NM , Morris R . Trophoblast in the circulating blood during pregnancy . Am J Obstet Gynecol . 1959;78:960–973
  3. Walknowska J , Conte FA , Grumbach MM . Practical and theoretical implications of fetal-maternal lymphocyte transfer . Lancet . 1969;i:1119–1122
  4. Schroder J , De la Chapelle A . Fetal lymphocytes in the maternal blood . Blood . 1972;39:153–162
  5. Covone AE , Mutton D , Johnson PM , Adinolfi M . Trophoblast cells in peripheral blood from pregnant women . Lancet . 1984;2:841–843
  6. Covone AE , Kozma R , Johnson PM , Latt SA , Adinolfi M . Analysis of peripheral maternal blood samples for the presence of placenta-derived cells using Y-specific probes and McAb H315 . Prenat Diagn . 1988;8:591–607
  7. Lo YM , Patel P , Wainscoat JS , Sampietro M , Gillmer MD , Fleming KA . Prenatal sex determination by DNA amplification from maternal peripheral blood . Lancet . 1989;2:1363–1365
  8. Mueller UW , Hawes CS , Wright AE , et al.   Isolation of fetal trophoblast cells from peripheral blood of pregnant women . Lancet . 1990;336:197–200
  9. Bianchi DW , Flint AF , Pizzimenti MF , Knoll JH , Latt SA . Isolation of fetal DNA from nucleated erythrocytes in maternal blood . Proc Natl Acad Sci USA . 1990;87:3279–3283
  10. Price JO , Elias S , Wachtel SS , et al.   Prenatal diagnosis with fetal cells isolated from maternal blood by multiparameter flow cytometry . Am J Obstet Gynecol . 1991;165:1731–1737
  11. Bianchi DW , Mahr A , Zickwolf GK , Houseal TW , Flint AF , Klinger KW . Detection of fetal cells with 47,XY,+21 karyo-type in maternal peripheral blood . Hum Genet . 1992;90:368–370
  12. Cacheux V , Milesi-Fluet C , Tachdjian G , et al.   Detection of 47,XYY trophoblast fetal cells in maternal blood by fluorescence in situ hybridization after using immunomagnetic lymphocyte depletion and flow cytometry sorting . Fetal Diagn Ther . 1992;7:190–194
  13. Ganshirt-Ahlert D , Borjesson-Stoll R , Burschyk M , et al.   Detection of fetal trisomies 21 and 18 from maternal blood using triple gradient and magnetic cell sorting . Am J Reprod Immunol . 1993;30:194–201
  14. Hamada H , Arinami T , Kubo T , Hamaguchi H , Iwasaki H . Fetal nucleated cells in maternal peripheral blood: frequency and relationship to gestational age . Hum Genet . 1993;91:427–432
  15. Takabayashi H , Kuwabara S , Ukita T , Ikawa K , Yamafuji K , Igarashi T . Development of non-invasive fetal DNA diagnosis from maternal blood . Prenat Diagn . 1995;15:74–77
  16. Sekizawa A , Kimura T , Sasaki M , Nakamura S , Kobayashi R , Sato T . Prenatal diagnosis of Duchenne muscular dystrophy using a single fetal nucleated erythrocyte in maternal blood . Neurology . 1996;46:1350–1353
  17. Bianchi DW , Simpson JL , Jackson LG , et al.   Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study . Prenat Diagn . 2002;22:609–615
  18. Kitagawa M , Sugiura K , Omi H , et al.   New technique using galactose-specific lectin for isolation of fetal cells from maternal blood . Prenat Diagn . 2002;22:17–21
  19. Holmes LB . Genetic counseling for the older pregnant woman: new data and questions . N Engl J Med . 1978;298:1419–1421
  20. Wald NJ , Cuckle HS , Densem JW , et al.   Maternal serum screening for Down's syndrome in early pregnancy . BMJ . 1988;297:883–887
  21. Resta RG . Changing demographics of advanced maternal age (AMA) and the impact on the predicted incidence of Down syndrome in the United States: implications for prenatal screening and genetic counseling . Am J Med Genet A . 2005;133:31–36
  22. Sekizawa A , Farina A , Okai T . Cell-free fetal DNA in plasma of pregnant women: clinical potential and origin . Taiwanese J Obstet Gynecol . 2005;44:116–122
  23. Benirschke K . Anatomical relationship between fetus and mother . Ann NY Acad Sci . 1994;731:9–20
  24. Ganshirt-Ahlert D , Basak N , Aidynli K , Holzgreve W . Fetal DNA in uterine vein blood . Obstet Gynecol . 1992;80:601–603
  25. Sargent IL , Choo YS , Redman CW . Isolating and analyzing fetal leukocytes in maternal blood . Ann NY Acad Sci . 1994;731:147–153
  26. Bertero MT , Camaschella C , Serra A , Bergui L , Cappio F . Circulating 'trophoblast' cells in pregnancy have maternal genetic markers . Prenat Diagn . 1988;8:585–590
  27. Henderson KG , Shaw TE , Barrett IJ , Telenius AH , Wilson RD , Kalousek DK . Distribution of mosaicism in human placentae . Hum Genet . 1996;97:650–654
  28. Goldberg JD , Wohlferd MM . Incidence and outcome of chromosomal mosaicism found at the time of chorionic villus sampling . Am J Obstet Gynecol . 1997;176:1349–1352
  29. Hawes CS, Suskin HA, Kalionis B, Mueller UW, Casey G, Hall J, et al. Detection of paternally inherited mutations for beta-thalassemia in trophoblast isolated from peripheral maternal blood . Ann NY Acad Sci . 1994;731:181–185
  30. Tse DB , Anderson P , Goldbard S , Gown AM , Hawes CS , Donnenfeld A . Characterization of trophoblast-reactive monoclonal antibodies by flow cytometry and their application for fetal cell isolation . Ann NY Acad Sci . 1994;731:162–169
  31. Grosset L , Barrelet V , Odartchenko N . Antenatal fetal sex determination from maternal blood during early pregnancy . Am J Obstet Gynecol . 1974;120:60–63
  32. Siebers JW , Knauf I , Hillemanns HG . Antenatal sex determination in blood from pregnant women . Humangenetik . 1975;28:273–280
  33. Parks DR , Herzenberg LA . Fetal cells from maternal blood: their selection and prospects for use in prenatal diagnosis . Methods Cell Biol . 1982;26:277–295
  34. Schindler AM , Martin-du-Pan R . Prenatal diagnosis of fetal lymphocytes in the maternal blood . Obstet Gynecol . 1972;40:340–346
  35. Takahara H , Kadotani T , Kusumi I , Makino S . Some critical aspects on prenatal diagnosis of sex in leucocyte cultures from pregnant women . Proc Jpn Acad . 1972;48:603–607
  36. Whang-Peng J , Leikin S , Harris C , Lee E , Sites J . The trans-placental passage of fetal leukocytes into the maternal blood . Proc Soc Exp Biol Med . 1973;142:50–53
  37. Schroder J . Are fetal cells in maternal blood mainly B lymphocytes? . Scand J Immunol . 1975;4:279–285
  38. Schroder J , Schroder E , Cann HM . Fetal cells in the maternal blood. Lack of response of fetal cells in maternal blood to mitogens and mixed leukocyte culture . Hum Genet . 1977;38:91–97
  39. Herzenberg LA , Bianchi DW , Schroder J , Cann HM , Iverson GM . Fetal cells in the blood of pregnant women: detection and enrichment by fluorescence-activated cell sorting . Proc Natl Acad Sci USA . 1979;76:1453–1455
  40. Iverson GM , Bianchi DW , Cann HM , Herzenberg LA . Detection and isolation of fetal cells from maternal blood using the flourescence-activated cell sorter (FACS) . Prenat Diagn . 1981;1:61–73
  41. Tharapel AT , Jaswaney VL , Dockter ME , et al.   Inability to detect fetal metaphases in flow-sorted lymphocyte cultures based on maternal-fetal HLA differences . Fetal Diagn Ther . 1993;8:95–101
  42. Schroder J , Tiilikainen A , De la Chapelle A . Fetal leukocytes in the maternal circulation after delivery. I. Cytological aspects . Transplantation . 1974;17:346–354
  43. Hsieh TT , Pao CC , Hor JJ , Kao SM . Presence of fetal cells in maternal circulation after delivery . Hum Genet . 1993;92:204–205
  44. Ciaranfi A , Curchod A , Odartchenko N . Post-partum survival of fetal lymphocytes in the maternal blood . Schweiz Med Wochenschr . 1977;107:134–138 (In German)
  45. Liou JD , Hsieh TT , Pao CC . Presence of cells of fetal origin in maternal circulation of pregnant women . Ann NY Acad Sci . 1994;731:237–241
  46. Bianchi DW , Zickwolf GK , Weil GJ , Sylvester S , DeMaria MA . Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum . Proc Natl Acad Sci USA . 1996;93:705–708
  47. Kleihauer E , Braun H , Betke K . Demonstration of fetal hemoglobin in erythrocytes of a blood smear . Klin Wochenschr . 1957;35:637–638 (In German)
  48. Clayton EM , Feldhaus WD , Whitacre FE . Fetal erythrocytes in the maternal circulation of pregnant women . Obstet Gynecol . 1964;23:915–919
  49. Ganshirt D , Garritsen H , Miny P , Holzgreve W . Fetal cells in maternal circulation throughout gestation . Lancet . 1994;343:1038–1039
  50. Pearson HA . Life-span of the fetal red blood cell . J Pediatr . 1967;70:166–171
  51. Holzgreve W , Garritsen HS , Ganshirt-Ahlert D . Fetal cells in the maternal circulation . J Reprod Med . 1992;37:410–418
  52. Von Koskull H , Gahmberg N . Fetal erythroblasts from maternal blood identified with 2,3-bisphosphoglycerate (BPG) and in situ hybridization (ISH) using Y-specific probes . Prenat Diagn . 1995;15:149–154
  53. Wachtel S , Elias S , Price J , et al.   Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction . Hum Reprod . 1991;6:1466–1469
  54. Miltenyi S , Muller W , Weichel W , Radbruch A . High gradient magnetic cell separation with MACS . Cytometry . 1990;11:231–238
  55. Ganshirt-Ahlert D , Pohlschmidt M , Gal A , Miny P , Horst J , Holzgreve W . Ratio of fetal to maternal DNA is less than 1 in 5000 at different gestational ages in maternal blood . Clin Genet . 1990;38:38–43
  56. Bianchi DW , Williams JM , Sullivan LM , Hanson FW , Klinger KW , Shuber AP . PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies . Am J Hum Genet . 1997;61:822–829
  57. Hamada H , Arinami T , Sohda S , Hamaguchi H , Kubo T . Midtrimester fetal sex determination from maternal peripheral blood by fluorescence in situ hybridization without enrichment of fetal cells . Prenat Diagn . 1995;15:78–81
  58. Slunga-Tallberg A , el-Rifai W , Keinanen M , et al.   Maternal origin of nucleated erythrocytes in peripheral venous blood of pregnant women . Hum Genet . 1995;96:53–57
  59. Slunga-Tallberg A , el-Rifai W , Keinanen M , et al.   Maternal origin of transferrin receptor positive cells in venous blood of pregnant women . Clin Genet . 1996;49:196–199
  60. de Graaf IM , Jakobs ME , Leschot NJ , Ravkin I , Goldbard S , Hoovers JM . Enrichment, identification and analysis of fetal cells from maternal blood: evaluation of a prenatal diagnosis system . Prenat Diagn . 1999;19:648–652
  61. Troeger C, Zhong XY, Burgemeister R, Minderer S, Tercanli S, Holzgreve W, et al. Approximately half of the erythroblasts in maternal blood are of fetal origin . Mol Hum Reprod . 1999;5:1162–1165
  62. Lo YM , Morey AL , Wainscoat JS , Fleming KA . Culture of fetal erythroid cells from maternal peripheral blood . Lancet . 1994;344:264–265
  63. Valerio D , Aiello R , Altieri V , Malato AP , Fortunato A , Canazio A . Culture of fetal erythroid progenitor cells from maternal blood for non-invasive prenatal genetic diagnosis . Prenat Diagn . 1996;16:1073–1082
  64. Bohmer RM , Johnson KL , Bianchi DW . Fetal and maternal progenitor cells in co-culture respond equally to erythropoietin . Prenat Diagn . 2001;21:818–823
  65. Campagnoli C, Roberts IA, Kumar S, Choolani M, Bennett PR, Letsky E, et al. Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis . Prenat Diagn . 2002;22:463–469
  66. Bonney EA , Matzinger P . The maternal immune system's interaction with circulating fetal cells . J Immunol . 1997;158:40–47
  67. Thomas MR , Williamson R , Craft I , Rodeck CH . The time of appearance, and quantitation, of fetal DNA in the maternal circulation . Ann NY Acad Sci . 1994;731:217–225
  68. Thomas MR , Williamson R , Craft I , Yazdani N , Rodeck CH . Y chromosome sequence DNA amplified from peripheral blood of women in early pregnancy . Lancet . 1994;343:413–414
  69. Lo YM , Patel P , Baigent CN , et al.   Prenatal sex determination from maternal peripheral blood using the polymerase chain reaction . Hum Genet . 1993;90:483–488
  70. Bianchi DW , Stewart JE , Garber MF , Lucotte G , Flint AF . Possible effect of gestational age on the detection of fetal nucleated erythrocytes in maternal blood . Prenat Diagn . 1991;11:523–528
  71. Ganshirt D , Borjesson-Stoll R , Burschyk M , et al.   Successful prenatal diagnosis from maternal blood with magnetic-activated cell sorting . Ann NY Acad Sci . 1994;731:103–114
  72. Rochelson B , Kaplan C , Guzman E , Arato M , Hansen K , Trunca C . A quantitative analysis of placental vasculature in the third-trimester fetus with autosomal trisomy . Obstet Gynecol . 1990;75:59–63
  73. Kuhlmann RS , Werner AL , Abramowicz J , Warsof SL , Arrington J . Levy DL Placental histology in fetuses between 18 and 23 weeks' gestation with abnormal karyotype . Am J Obstet Gynecol . 1990;163:1264–1270
  74. Sipes SL , Weiner CP , Wenstrom KD , Williamson RA , Grant SS . The association between fetal karyotype and mean corpuscular volume . Am J Obstet Gynecol . 1991;165:1371–1376
  75. Thilaganathan B , Meher-Homji NJ , Nicolaides KH . Blood transferrin receptor expression in chromosomally abnormal fetuses . Prenat Diagn . 1995;15:282–284
  76. Zheng YL , Zhen DK , DeMaria MA , et al.   Search for the optimal fetal cell antibody: results of immunophenotyping studies using flow cytometry . Hum Genet . 1997;100:35–42
  77. Simpson JL , Elias S . Isolating fetal cells from maternal blood. Advances in prenatal diagnosis through molecular technology . JAMA . 1993;270:2357–2361
  78. Holzgreve W , Ghezzi F , Di Naro E , Ganshirt D , Maymon E , Hahn S . Disturbed feto-maternal cell traffic in preeclampsia . Obstet Gynecol . 1998;91:669–672
  79. Nelson JL , Furst DE , Maloney S , et al.   Microchimerism and HLA-compatible relationships of pregnancy in scleroderma . Lancet . 1998;351:559–562
  80. DeMaria MA , Zheng YL , Zhen D , Weinschenk NM , Vadnais TJ , Bianchi DW . Improved fetal nucleated erythrocyte sorting purity using intracellular antifetal hemoglobin and Hoechst 33342 . Cytometry . 1996;25:37–45
  81. Sekizawa A, Farina A, Zhen DK, Wang JY, Falco VM, Elmes S, et al. Improvement of fetal cell recovery from maternal blood: suitable density gradient for FACS separation . Fetal Diagn Ther . 1999;14:229–233
  82. Ganshirt-Ahlert D , Burschyk M , Garritsen HS , et al.   Magnetic cell sorting and the transferrin receptor as potential means of prenatal diagnosis from maternal blood . Am J Obstet Gynecol . 1992;166:1350–1355
  83. Bigbee WL , Grant SG . Use of allele-specific glycophorin A antibodies to enumerate fetal erythroid cells in maternal circulation . Ann NY Acad Sci . 1994;731:128–132
  84. Busch J , Huber P , Holtz J , Pfluger E , Radbruch A . Simple and fast “double-MACS” sorting of fetal erythroblasts from maternal blood for PCR-based paternity analysis . Ann NY Acad Sci . 1994;731:144–146
  85. Zhen DK , Wang JY , Falco VM , Weber W , Delli-Bovi L , Bianchi DW . Poly-FISH: a technique of repeated hybridizations that improves cytogenetic analysis of fetal cells in maternal blood . Prenat Diagn . 1998;18:1181–1185
  86. Wang JY, Zhen DK, Falco VM, Farina A, Zheng YL, Delli-Bovi LC, et al. Fetal nucleated erythrocyte recovery: fluorescence activated cell sorting-based positive selection using anti-gamma globin versus magnetic activated cell sorting using anti-CD45 depletion and anti-gamma globin positive selection . Cytometry . 2000;39:224–230
  87. Sekizawa A , Samura O , Zhen DK , Falco V , Farina A , Bianchi DW . Apoptosis in fetal nucleated erythrocytes circulating in maternal blood . Prenat Diagn . 2000;20:886–889
  88. Sekizawa A , Samura O , Zhen DK , Falco V , Bianchi DW . Fetal cell recycling: diagnosis of gender and RhD geno-type in the same fetal cell retrieved from maternal blood . Am J Obstet Gynecol . 1999;181:1237–1242
  89. Samura O , Sekizawa A , Zhen DK , Falco VM , Bianchi DW . Comparison of fetal cell recovery from maternal blood using a high density gradient for the initial separation step: 1. 090 versus 1.119 g/ml . Prenat Diagn . 2000;20:281–286
  90. Bhat NM , Bieber MM , Teng NN . One-step enrichment of nucleated red blood cells. A potential application in perinatal diagnosis . J Immunol Methods . 1993;158:277–280
  91. Voullaire L , Ioannou P , Nouri S , Williamson R . Fetal nucleated red blood cells from CVS washings: an aid to development of first trimester non-invasive prenatal diagnosis . Prenat Diagn . 2001;21:827–834
  92. Troeger C , Holzgreve W , Hahn S . A comparison of different density gradients and antibodies for enrichment of fetal erythroblasts by MACS . Prenat Diagn . 1999;19:521–526
  93. Prieto B, Alonso R, Paz A, Candenas M, Venta R, Ladenson JH, et al. Optimization of nucleated red blood cell (NRBC) recovery from maternal blood collected using both layers of a double density gradient . Prenat Diagn . 2001;21:187–193
  94. Boyer SH , Noyes AN , Boyer ML . Enrichment of erythrocytes of fetal origin from adult-fetal blood mixtures via selective hemolysis of adult blood cells: an aid to antenatal diagnosis of hemoglobinopathies . Blood . 1976;47:883–897
  95. Hengstschlager M , Bernaschek G . Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection . FEBS Lett . 1997;404:299–302
  96. Savion S, Carp H, Shepshelovich J, Irlin J, Kostykov M, Fein A, et al. Use of antibodies against the human antigen of erythroblasts for the detection of nucleated erythrocytes in the maternal circulation . Biol Neonate . 1997;71:126–130
  97. Valerio D , Aiello R , Altieri V . Isolation of fetal erythroid cells from maternal blood based on expression of erythropoietin receptors . Mol Hum Reprod . 1997;3:451–455
  98. Wachtel SS , Sammons D , Manley M , et al.   Fetal cells in maternal blood: recovery by charge flow separation . Hum Genet . 1996;98:162–166
  99. Wachtel SS, Sammons D, Twitty G, Utermohlen J, Tolley E, Phillips O, et al. Charge flow separation: quantification of nucleated red blood cells in maternal blood during pregnancy . Prenat Diagn . 1998;18:455–463
  100. Babochkina T , Mergenthaler S , Lapaire O , et al.   Evaluation of a soybean lectin-based method for the enrichment of erythroblasts . J Histochem Cytochem . 2005;53:329–330
  101. Zheng YL , Carter NP , Price CM , et al.   Prenatal diagnosis from maternal blood: simultaneous immunophenotyping and FISH of fetal nucleated erythrocytes isolated by negative magnetic cell sorting . J Med Genet . 1993;30:1051–1056
  102. Ferguson-Smith MA , Zheng YL , Carter NP . Simultaneous immunophenotyping and FISH on fetal cells from maternal blood . Ann NY Acad Sci . 1994;731:73–79
  103. Samura O , Pertl B , Sohda S , et al.   Female fetal cells in maternal blood: use of DNA polymorphisms to prove origin . Hum Genet . 2000;107:28–32
  104. Kondo T , Sekizawa A , Saito H , Jimbo M , Sugito Y , Okai T . Fate of fetal nucleated erythrocytes circulating in maternal blood: apoptosis is induced by maternal oxygen concentration . Clin Chem . 2002;48:1618–1620
  105. Babochkina T, Mergenthaler S, De Napoli G, Hristoskova S, Tercanli S, Holzgreve W, et al. Numerous erythroblasts in maternal blood are impervious to fluorescent in situ hybridization analysis, a feature related to a dense compact nucleus with apoptotic character . Haematologica . 2005;90:740–745
  106. Watanabe A, Sekizawa A, Taguchi A, Saito H, Yanaihara T, Shimazu M, et al. Prenatal diagnosis of ornithine transcarbamylase deficiency by using a single nucleated erythrocyte from maternal blood . Hum Genet . 1998;102:611–615
  107. Cheung MC , Goldberg JD , Kan YW . Prenatal diagnosis of sickle cell anaemia and thalassaemia by analysis of fetal cells in maternal blood . Nat Genet . 1996;14:264–268

PII: S1028-4559(09)60184-4

doi: 10.1016/S1028-4559(09)60184-4

Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 1 , Pages 10-20 , March 2006

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