title: Early Prediction of Hypertensive Disorders of Pregnancy Using Cell-Free Fetal DNA, Cell-Free Total DNA, and Biochemical Markers.
abstract: OBJECTIVE
  To evaluate the predictive value of separate and combined tests using cell-free fetal DNA (cffDNA), cell-free total DNA (cfDNA), and biochemical markers for the early detection of pregnancies with hypertensive disorders.
  
  
  METHODS
  A nested case-control study was conducted with 135 singleton pregnancies including 17 gestational hypertension cases, 34 preeclampsia (PE) cases, and 84 controls. We performed real-time quantitative PCR to measure levels of DSCR3 and RASSF1A as cffDNA markers and HYP2 as a cfDNA marker in the first and early second trimesters. Levels of pregnancy-associated plasma protein A (PAPP-A), α-fetoprotein, β-human chorionic gonadotropin, unconjugated estriol, and inhibin A were also determined.
  
  
  RESULTS
  Compared with controls, the median levels and multiples of the median (MoM) values of HYP2 were significantly higher in the PE and hypertensive disorders of pregnancy (HDP) groups at 6-14 and 15-23 weeks. Frist-trimester PAPP-A MoM was significantly lower in PE and HDP than in controls. For PE and HDP, the best model included the first-trimester DSCR3, HYP2, and PAPP-A MoM values achieving detection rates of 67 and 58% at a fixed 10% false-positive rate, respectively [area under the receiver operating characteristic curve 0.832 (95% CI 0.689-0.928) for PE; 0.751 (0.607-0.863) for HDP].
  
  
  CONCLUSIONS
  The study demonstrates the potential utility of combined first-trimester cffDNA, cfDNA, and PAPP-A for the early prediction of PE.
authors.affiliation: Laboratory of Medical Genetics, Medical Research Institute, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
authors.forename: Yoo Jung
authors.initials: YJ
authors.lastname: Han
authors.forename: June Seek
authors.initials: JS
authors.lastname: Choi
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Ryu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004247:DNA / Q000097:blood; D042241:Early Diagnosis; D057890:Epigenomics; D004964:Estriol / Q000097:blood; D005260:Female; D005865:Gestational Age; D006801:Humans; D046110:Hypertension, Pregnancy-Induced; D007265:Inhibins / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D062145:Maternal Serum Screening Tests / Q000379:methods*; D011225:Pre-Eclampsia / Q000175:diagnosis; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis*; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000097:blood; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C110162:VPS26C protein, human; D000509:alpha-Fetoproteins; C422362:inhibin A; D007265:Inhibins; D004247:DNA; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human; D004964:Estriol