title: Screening for trisomies 21, 18 and 13 by cell-free DNA analysis of maternal blood at 10-11 weeks' gestation and the combined test at 11-13 weeks.
abstract: OBJECTIVE
  To examine in a general population the performance of cell-free DNA (cfDNA) testing for trisomies 21, 18 and 13 at 10-11 weeks' gestation and compare it to that of the combined test at 11-13 weeks.
  
  
  METHODS
  In 2905 singleton pregnancies, prospective screening for trisomies was performed by chromosome-selective sequencing of cfDNA in maternal blood at 10-11 weeks' gestation and by the combined test at 11-13 weeks' gestation.
  
  
  RESULTS
  Median maternal age of the study population was 36.9 (range, 20.4-51.9) years. Results from cfDNA analysis were provided for 2851 (98.1%) cases and these were available within 14 days from sampling in 2848 (98.0%) cases. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or clinical examination of the neonates. Of the 2785 pregnancies with a cfDNA result and known trisomic status, cfDNA testing correctly identified all 32 cases with trisomy 21, nine of 10 with trisomy 18 and two of five with trisomy 13, with false-positive rates of 0.04%, 0.19% and 0.07%, respectively. In cases with discordant results between cfDNA testing and fetal karyotype, the median fetal fraction was lower than in those with concordant results (6% vs 11%). Using the combined test, the estimated risk for trisomy 21 was ≥ 1/100 in all trisomic cases and in 4.4% of the non-trisomic pregnancies.
  
  
  CONCLUSIONS
  The performance of first-trimester cfDNA testing for trisomies 21 and 18 in the general population is similar to that in high-risk pregnancies. Most false-positive and false-negative results from cfDNA testing could be avoided if the a priori risk from the combined test is taken into account in the interpretation of individual risk.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Quezada
authors.forename: M M
authors.initials: MM
authors.lastname: Gil
authors.forename: C
authors.initials: C
authors.lastname: Francisco
authors.forename: G
authors.initials: G
authors.lastname: Oròsz
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D002474:Cell-Free System; D002882:Chromosomes, Human, Pair 13 / Q000378:metabolism*; D002887:Chromosomes, Human, Pair 18 / Q000378:metabolism*; D002891:Chromosomes, Human, Pair 21 / Q000378:metabolism*; D003657:Decision Making; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D062145:Maternal Serum Screening Tests; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011296:Prenatal Diagnosis; D012680:Sensitivity and Specificity; D014314:Trisomy / Q000175:diagnosis*
keywords: cell-free DNA; combined test; fetal fraction; first trimester; prenatal diagnosis; screening; trisomies