title: Circulating cell-free fetal nucleic acid analysis may be a novel marker of fetomaternal hemorrhage after elective first-trimester termination of pregnancy.
abstract: Analysis of cell-free fetal DNA (fDNA) and RNA in maternal plasma could be useful in the diagnosis and management of complications of pregnancy. In this review, we discuss our studies to investigate the potential of fetal nucleic acid measurement in maternal plasma as a marker of fetomaternal hemorrhage (FMH) after elective first-trimester termination of pregnancy (TOP). Using quantitative real-time PCR amplification of the DYS1 sequence, elevation of plasma fDNA levels after TOP was observed, especially in the late first trimester. This corresponds with the functional development of the placental vascular structure and fetal hematopoiesis. This Y sequence-based PCR amplification assay, however, limits the analysis to pregnant women carrying male fetuses. Therefore, we also developed a real-time quantitative reverse-transcriptase PCR assay of the gamma-globin transcript as a marker of fetal erythroid cells. Although plasma gamma-globin mRNA levels were decreased after TOP in many patients, an elevation was observed in some patients at greater than 9 weeks' gestation, which is consistent with the increase in plasma fDNA levels. Our data suggest that fetal hematopoietic cells contribute to the pool of fetal nucleic acids in the maternal circulation. Measurement of cell-free fetal nucleic acid levels in maternal plasma may have clinical application as a novel marker of FMH after 9 weeks of gestation.
authors.affiliation: Division of Genetics, Department of Pediatrics, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
authors.forename: Tuangsit
authors.initials: T
authors.lastname: Wataganara
authors.forename: Erik S
authors.initials: ES
authors.lastname: Leshane
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Chen
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: Inga
authors.initials: I
authors.lastname: Peter
authors.forename: Lynn
authors.initials: L
authors.lastname: Borgatta
authors.forename: Kirby L
authors.initials: KL
authors.lastname: Johnson
authors.forename: Diana W
authors.initials: DW
authors.lastname: Bianchi
mesh_terms: D000028:Abortion, Induced; D015415:Biomarkers / Q000097:blood*; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005331:Fetomaternal Transfusion / Q000097:blood*; D005914:Globins / Q000235:genetics; D006801:Humans; D009696:Nucleic Acids / Q000097:blood* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D012313:RNA / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D015415:Biomarkers; D009696:Nucleic Acids; D012333:RNA, Messenger; D012313:RNA; D005914:Globins; D004247:DNA