Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 2 , Pages 116-122, June 2005

Cell-Free Fetal DNA in Plasma of Pregnant Women: Clinical Potential and Origin

  • Akihiko Sekizawa

      Affiliations

    • Corresponding Author InformationCorrespondence to: Dr. Akihiko Sekizawa, Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo, 142-8666, Japan
    • ,
  • Antonio Farina
    • ,
  • Takashi Okai

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

Received 17 January 2005; received in revised form 26 January 2005; accepted 26 January 2005.

Article Outline

Summary

Circulating fetal DNA in maternal plasma can be used for both fetal genetic testing and evaluation of complications of pregnancy. As a prenatal genetic test, the greatest advantage of using circulating fetal DNA is the lack of risk. This approach has been applied to the diagnosis of fetal gender, fetal Rhesus D (RhD) blood type, and fetal single-gene disorders. However, it only allows examination of disorders where the gene of interest is present in the fetal genome but absent from maternal DNA. Since most fetal DNA probably originates from villous trophoblasts, concentrations can be used to evaluate damage to trophoblasts, particularly in pathologic complications of pregnancy such as pre-eclampsia, invasive placenta, hyperemesis gravidarum, and trisomy 21. Fetal DNA in the plasma of pregnant women thus offers a new source of data that can be used in various clinical settings.

Key Words:  fetal DNA , genetic testing , plasma

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Teshima IE , Kalousek DK , Vekemans MJ , et al.   Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples . Prenat Diagn . 1992;12:443–466
  2. 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
  3. 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
  4. Sekizawa A , Samura O , Zhen DK , Falco V , Bianchi DW . Fetal cell recycling: diagnosis of gender and RhD genotype in the same fetal cell retrieved from maternal blood . Am J Obstet Gynecol . 1999;181:1237–1242
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. Bianchi DW , Simpson JL , Jackson LG , et al.   Fetal cells in maternal blood: NIFTY clinical trial interim analysis. DMSTAT. NICHD fetal cell study (NIFTY) group . Prenat Diagn . 1999;19:994–995
  11. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, et al. Presence of fetal DNA in maternal plasma and serum . Lancet . 1997;350:485–487
  12. Lo YM , Tein MS , Lau TK , et al.   Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis . Am J Hum Genet . 1998;62:768–775
  13. Sekizawa A, Kondo T, Iwasaki M, Watanabe A, Jimbo M, Saito H, et al. Accuracy of fetal gender determination by analysis of DNA in maternal plasma . Clin Chem . 2001;47:1856–1858
  14. Lo YM , Zhang J , Leung TN , Lau TK , Chang AM , Hjelm NM . Rapid clearance of fetal DNA from maternal plasma . Am J Hum Genet . 1999;64:218–224
  15. Lo YM , Hjelm NM , Fidler C , et al.   Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma . N Engl J Med . 1998;339:1734–1738
  16. Saito H , Sekizawa A , Morimoto T , Suzuki M , Yanaihara T . Prenatal DNA diagnosis of a single-gene disorder from maternal plasma . Lancet . 2000;356:1170
  17. Shiang R , Thompson LM , Zhu YZ , et al.   Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia . Cell . 1994;78:335–342
  18. Amicucci P , Gennarelli M , Novelli G , Dallapiccola B . Prenatal diagnosis of myotonic dystrophy using fetal DNA obtained from maternal plasma . Clin Chem . 2000;46:301–302
  19. Gonzalez-Gonzalez MC , Garcia-Hoyos M , Trujillo MJ , et al.   Prenatal detection of a cystic fibrosis mutation in fetal DNA from maternal plasma . Prenat Diagn . 2002;22:946–948
  20. Chiu RW , Lau TK , Leung TN , Chow KC , Chui DH , Lo YM . Prenatal exclusion of beta thalassaemia major by examination of maternal plasma . Lancet . 2002;360:998–1000
  21. Chiu RW , Lau TK , Cheung PT , Gong ZQ , Leung TN , Lo YM . Noninvasive prenatal exclusion of congenital adrenal hyperplasia by maternal plasma analysis: a feasibility study . Clin Chem . 2002;48:778–780
  22. Lo YM , Leung TN , Tein MS , et al.   Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia . Clin Chem . 1999;45:184–188
  23. Zhong XY , Holzgreve W , Hahn S . Circulatory fetal and maternal DNA in pregnancies at risk and those affected by preeclampsia . Ann NY Acad Sci . 2001;945:138–140
  24. Sekizawa A, Jimbo M, Saito H, Iwasaki M, Matsuoka R, Okai T, et al. Cell-free fetal DNA in the plasma of pregnant women with severe fetal growth restriction . Am J Obstet Gynecol . 2003;188:480–484
  25. Caramelli E , Rizzo N , Concu M , et al.   Cell-free fetal DNA concentration in plasma of patients with abnormal uterine artery Doppler waveform and intrauterine growth restriction – a pilot study . Prenat Diagn . 2003;23:367–371
  26. Roberts JM , Cooper DW . Pathogenesis and genetics of preeclampsia . Lancet . 2001;357:53–56
  27. Sekizawa A , Yokokawa K , Sugito Y , et al.   Evaluation of bidirectional transfer of plasma DNA through placenta . Hum Genet . 2003;113:307–310
  28. Sekizawa A , Farina A , Koide K , et al.   Beta-globin DNA in maternal plasma as a molecular marker of preeclampsia . Prenat Diagn . 2004;24:697–700
  29. Leung TN , Zhang J , Lau TK , Chan LY , Lo YM . Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia . Clin Chem . 2001;47:137–139
  30. Farina A , Sekizawa A , Iwasaki M , Matsuoka R , Ichizuka K , Okai T . Total cell-free DNA (beta-globin gene) distribution in maternal plasma at the second trimester: a new prospective for preeclampsia screening . Prenat Diagn . 2004;24:722–726
  31. Sekizawa A , Sugito Y , Iwasaki M , et al.   Cell-free fetal DNA is increased in plasma of women with hyperemesis gravidarum . Clin Chem . 2001;47:2164–2165
  32. Sugito Y , Sekizawa A , Farina A , et al.   Relationship between severity of hyperemesis gravidarum and fetal DNA concentration in maternal plasma . Clin Chem . 2003;49:1667–1669
  33. Minagawa M , Narita J , Tada T , et al.   Mechanisms underlying immunologic states during pregnancy: possible association of the sympathetic nervous system . Cell Immunol . 1999;196:1–13
  34. Sekizawa A , Jimbo M , Saito H , et al.   Increased cell-free fetal DNA in plasma of two women with invasive placenta . Clin Chem . 2002;48:353–354
  35. Jimbo M, Sekizawa A, Sugito Y, Matsuoka R, Ichizuka K, Saito H, et al. Placenta increta: postpartum monitoring of plasma cell-free fetal DNA . Clin Chem . 2003;49:1540–1541
  36. Leung TN , Zhang J , Lau TK , Hjelm NM , Lo YM . Maternal plasma fetal DNA as a marker for preterm labour . Lancet . 1998;352:1904–1905
  37. Farina A, LeShane E, Romero R, Gomez R, Chaiworapongsa T, Rizzo N, et al. High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery . Am J Obstet Gynecol . 2005; [In press]
  38. Lo YM , Lau TK , Zhang J , et al.   Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21 . Clin Chem . 1999;45:1747–1751
  39. Zhong XY , Burk MR , Troeger C , Jackson LR , Holzgreve W , Hahn S . Fetal DNA in maternal plasma is elevated in pregnancies with aneuploid fetuses . Prenat Diagn . 2000;20:795–798
  40. Farina A , LeShane ES , Lambert-Messerlian GM , et al.   Evaluation of cell-free fetal DNA as a second-trimester maternal serum marker of Down syndrome pregnancy . Clin Chem . 2003;49:239–242
  41. Ohashi Y , Miharu N , Honda H , Samura O , Ohama K . Quantitation of fetal DNA in maternal serum in normal and aneuploid pregnancies . Hum Genet . 2000;108:123–127
  42. 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
  43. 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
  44. Angert RM , LeShane ES , Lo YM , Chan LY , Delli-Bovi LC , Bianchi DW . Fetal cell-free plasma DNA concentrations in maternal blood are stable 24 hours after collection: analysis of first- and third-trimester samples . Clin Chem . 2003;49:195–198
  45. Al-Mufti R , Lees C , Albaiges G , Hambley H , Nicolaides KH . Fetal cells in maternal blood of pregnancies with severe fetal growth restriction . Hum Reprod . 2000;15:218–221
  46. Hoesli I , Danek M , Lin D , Li Y , Hahn S , Holzgreve W . Circulating erythroblasts in maternal blood are not elevated before onset of preterm labor . Obstet Gynecol . 2002;100:992–996
  47. Loke YW , King A . Immunology of human placental implantation: clinical implications of our current understanding . Mol Med Today . 1997;3:153–159
  48. Ishihara N , Matsuo H , Murakoshi H , Laoag-Fernandez JB , Samoto T , Maruo T . Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation . Am J Obstet Gynecol . 2002;186:158–166

PII: S1028-4559(09)60122-4

doi:10.1016/S1028-4559(09)60122-4

Taiwanese Journal of Obstetrics and Gynecology
Volume 44, Issue 2 , Pages 116-122, June 2005

Article Tools