Obstetrics & Gynecology

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Obstetrics & Gynecology:
doi: 10.1097/AOG.0000000000000863
Contents: Original Research

Use of Cell-Free DNA in the Investigation of Intrauterine Fetal Demise and Miscarriage

Clark-Ganheart, Cecily A. MD; Fries, Melissa H. MD; Leifheit, Kathryn M. MSPH; Jensen, Taylor J. PhD; Moreno-Ruiz, Nilda L. MD, MPH; Ye, Peggy P. MD, MPH; Jennings, Jacky M. PhD, MPH; Driggers, Rita W. MD

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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.

CONCLUSION: 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.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928.

LEVEL OF EVIDENCE: III

© 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

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