title: Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test.
abstract: OBJECTIVE
  We sought to determine the ability of single-nucleotide polymorphism-based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies.
  
  
  METHODS
  The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced. Sequencing results were analyzed to determine fetal chromosome copy number and to identify the presence of additional fetal haplotypes.
  
  
  RESULTS
  Additional fetal haplotypes, indicative of fetal triploidy, vanishing twin, or undetected twin pregnancy, were identified in 130 (0.42%) cases. Clinical confirmation (karyotype for singleton pregnancies, ultrasound for multifetal pregnancies) was available for 58.5% (76/130) of cases. Of the 76 cases with confirmation, 42.1% were vanishing twin, 48.7% were viable twin, 5.3% were diandric triploids, and 3.9% were nontriploid pregnancies that lacked evidence of co-twin demise. One pregnancy had other indications suggesting triploidy but lacked karyotype confirmation. Of the 5 vanishing twin cases with a known date of demise, 100% of losses occurred in the first trimester; up to 8 weeks elapsed between loss and detection by NIPT.
  
  
  CONCLUSIONS
  This single-nucleotide polymorphism-based NIPT successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. As vanishing twins are more likely to be aneuploid, and undetected residual cell-free DNA could bias NIPT results, the ability of this method to identify additional fetal haplotypes is expected to result in fewer false-positive calls and prevent incorrect fetal sex calls.
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Kirsten J
authors.initials: KJ
authors.lastname: Curnow
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
authors.forename: Louise
authors.initials: L
authors.lastname: Wilkins-Haug
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Eser
authors.initials: E
authors.lastname: Kırkızlar
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Stosic
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hall
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.affiliation: Natera, San Carlos, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
authors.affiliation: Natera, San Carlos, CA. Electronic address: sgross@natera.com.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gross
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005327:Fetal Resorption / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D006828:Hydatidiform Mole / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods*; D057885:Triploidy; D055815:Young Adult
keywords: noninvasive prenatal testing; single-nucleotide polymorphism; triploidy; vanishing twin