Fetal DNA detection in maternal plasma throughout gestation
- 345 Downloads
The presence of fetal DNA in maternal plasma may represent a source of genetic material which can be obtained noninvasively. We wanted to assess whether fetal DNA is detectable in all pregnant women, to define the range and distribution of fetal DNA concentration at different gestational ages, to identify the optimal period to obtain a maternal blood sample yielding an adequate amount of fetal DNA for prenatal diagnosis, and to evaluate accuracy and predictive values of this approach. This information is crucial to develop safe and reliable non-invasive genetic testing in early pregnancy and monitoring of pregnancy complications in late gestation. Fetal DNA quantification in maternal plasma was carried out by real-time PCR on the SRY gene in male-bearing pregnancies to distinguish between maternal and fetal DNA. A cohort of 1,837 pregnant women was investigated. Fetal DNA could be detected from the sixth week and could be retrieved at any gestational week. No false-positive results were obtained in 163 women with previous embryo loss or previous male babies. Fetal DNA analysis performed blindly on a subset of 464 women displayed 99.4, 97.8 and 100% accuracy in fetal gender determination during the first, second, and third trimester of pregnancy, respectively. No SRY amplification was obtained in seven out of the 246 (2.8%) male-bearing pregnancies. Fetal DNA from maternal plasma seems to be an adequate and reliable source of genetic material for a noninvasive prenatal diagnostic approach.
KeywordsBlood Group Prenatal Diagnosis Maternal Plasma Female Fetus Fetal Gender
This work was supported by Telethon, Project number GGP02015 (L.C.), MIUR Cofin 2002 (A.F.).
- Atkinson AC (1980) A note on the generalized information criterion for the choice of a model. Biometrika 67:413–418Google Scholar
- Chiu RW, Poon LL, Lau TK, Leung TN, Wong EM, Lo YM (2001) Effects of blood-processing protocols on fetal and total DNA quantification in maternal plasma. Clin Chem 47:1607–1613Google Scholar
- Cremonesi L, Galbiati S, Foglieni B, Smid M, Gambini D, Ferrari A, Viora E, Campogrande M, Pagliano M, Travi M, Piga A, Restagno G, Ferrari M (2004) Feasibility study for a microchip-based approach for noninvasive prenatal diagnosis of genetic diseases. Ann NY Acad Sci 1022:105–112CrossRefPubMedGoogle Scholar
- Ding C, Chiu RW, Lau TK, Leung TN, Chan LC, Chan AY, Charoenkwan P, Ng IS, Law HY, Ma ES, Xu X, Wanapirak C, Sanguansermsri T, Liao C, Ai MA, Chui DH, Cantor CR, Lo YM (2004) MS analysis of single-nucleotide differences in circulating nucleic acids: application to noninvasive prenatal diagnosis. Proc Natl Acad Sci USA 101:10762–10767CrossRefPubMedGoogle Scholar
- Johnson KL, Dukes KA, Vidaver J, LeShane ES, Ramirez I, Weber WD, Bischoff FZ, Hahn S, Sharma A, Dang DX, Hire LM, Bianchi DW, Simpson JL, Holzgreve W, Elias S, Klinger KW (2004) Interlaboratory comparison of fetal male DNA detection from common maternal plasma samples by real-time PCR. Clin Chem 50:516–521CrossRefPubMedGoogle Scholar
- Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW (1999a) Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. Clin Chem 45:1747–1751Google Scholar
- Nasis O, Thompson S, Hong T, Sherwood M, Radcliffe S, Jackson L, Otevrel T (2004) Improvement in sensitivity of allele-specific PCR facilitates reliable noninvasive prenatal detection of cystic fibrosis. Clin Chem 50:694–701Google Scholar
- R Development Core Team (2004) A language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- Rijnders RJ, Christiaens GC, Soussan AA, van der Schoot CE (2004) Cell-free fetal DNA is not present in plasma of nonpregnant mothers. Clin Chem 50:679–681 (author reply 681)Google Scholar
- Sekizawa A, Kondo T, Iwasaki M, Watanabe A, Jimbo M, Saito H, Okai T (2001) Accuracy of fetal gender determination by analysis of DNA in maternal plasma. Clin Chem 47:1856–1858Google Scholar
- Smid M, Galbiati S, Vassallo A, Gambini D, Ferrari A, Viora E, Pagliano M, Restagno G, Ferrari M, Cremonesi L (2003b) No evidence of fetal DNA persistence in maternal plasma after pregnancy. Hum Genet 112:617–618Google Scholar