title: Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis.
abstract: Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. bischoff@bcm.tmc.edu
authors.forename: Farideh Z
authors.initials: FZ
authors.lastname: Bischoff
authors.forename: Mina K
authors.initials: MK
authors.lastname: Sinacori
authors.forename: Dianne D
authors.initials: DD
authors.lastname: Dang
authors.forename: Deborah
authors.initials: D
authors.lastname: Marquez-Do
authors.forename: Cassandra
authors.initials: C
authors.lastname: Horne
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
mesh_terms: D000782:Aneuploidy; D002869:Chromosome Aberrations; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005333:Fetus / Q000166:cytology*; D005865:Gestational Age; D006801:Humans; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis
chemical_list: D004247:DNA