title: Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.
abstract: OBJECTIVE
  To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting.
  
  
  METHODS
  We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities.
  
  
  RESULTS
  Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result.
  
  
  CONCLUSIONS
  Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks.
  
  
  BACKGROUND
  ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928.
  
  
  METHODS
  III.
authors.affiliation: Department of Obstetrics and Gynecology, MedStar Washington Hospital Center/MedStar Georgetown University Hospital, and the Department of Obstetrics and Gynecology, Johns Hopkins Medicine at Sibley Memorial Hospital, Washington, DC; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and Research and Development, Sequenom Laboratories, San Diego, California.
authors.forename: Cecily A
authors.initials: CA
authors.lastname: Clark-Ganheart
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Fries
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Leifheit
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Jensen
authors.forename: Nilda L
authors.initials: NL
authors.lastname: Moreno-Ruiz
authors.forename: Peggy P
authors.initials: PP
authors.lastname: Ye
authors.forename: Jacky M
authors.initials: JM
authors.lastname: Jennings
authors.forename: Rita W
authors.initials: RW
authors.lastname: Driggers
mesh_terms: D000030:Abortion, Missed / Q000097:blood* / Q000000981:diagnostic imaging; D000328:Adult; D004247:DNA / Q000097:blood*; D005260:Female; D005313:Fetal Death; D005865:Gestational Age; D006801:Humans; D007621:Karyotyping; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011262:Pregnancy Trimester, Second / Q000097:blood; D011263:Pregnancy Trimester, Third / Q000097:blood; D011446:Prospective Studies; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics; D016216:Ultrasonography, Prenatal; D055815:Young Adult
chemical_list: D004247:DNA