title: Fetal fraction estimate in twin pregnancies using directed cell-free DNA analysis.
abstract: OBJECTIVE
  To estimate fetal fraction (FF) in monozygotic and dizygotic twin pregnancies.
  
  
  METHODS
  Maternal plasma samples were obtained from 35 monochorionic twin pregnancies with male fetuses (monozygotic) and 35 dichorionic pregnancies discordant for fetal sex (dizygotic) at 11-13 weeks' gestation. Cell-free DNA was extracted and chromosome-selective sequencing with digital analysis of selected regions (DANSR™) was carried out. The fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate FF using polymorphic alleles. In dizygotic twins the FORTE algorithm was modified to estimate the smallest FF contribution of the 2 fetuses. In both types of twins, FF was also determined by analysis of Y-chromosome sequences.
  
  
  RESULTS
  In monozygotic twins, the median total FF was 14.0% (range 8.2-27.0%) and in dizygotic twins the median smallest FF was 7.9% (4.9-14.0%). There were significant associations in FF between the methods using polymorphic alleles and Y-chromosome sequences for both monozygotic (r=0.951, p<0.0001) and dizygotic (r=0.743, p<0.0001) twins.
  
  
  CONCLUSIONS
  The study demonstrates the feasibility of an approach for cfDNA testing in twin pregnancies. This involves estimation of total FF in monozygotic twins and estimation of the lower FF of the 2 fetuses in dizygotic twins.
authors.affiliation: Ariosa Diagnostics, Inc., San Jose, Calif., USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Struble
authors.forename: Argyro
authors.initials: A
authors.lastname: Syngelaki
authors.forename: Arnold
authors.initials: A
authors.lastname: Oliphant
authors.forename: Ken
authors.initials: K
authors.lastname: Song
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D002474:Cell-Free System / Q000502:physiology; D004247:DNA / Q000235:genetics*; D005260:Female; D005865:Gestational Age; D006801:Humans; D008297:Male; D062145:Maternal Serum Screening Tests / Q000379:methods*; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D004247:DNA