title: Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact.
abstract: OBJECTIVE
  To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study).
  
  
  METHODS
  Women with elevated risk based on first trimester combined testing (FCT ≥ 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome.
  
  
  RESULTS
  Between 1 April and 1 September 2014, 1413/23 232 (6%) women received a high-risk FCT result. Of these, 1211 (85.7%) chose NIPT. One hundred seventy-nine women had NIPT based on medical history. In total, 1386/1390 (99.7%) women received a result, 6 (0.4%) after redraw. Mean turn-around time was 14 days. Follow-up was available in 1376 (99.0%) pregnancies. NIPT correctly predicted 37/38 (97.4%) trisomies 21, 18 or 13 (29/30, 4/4 and 4/4 respectively); 5/1376 (0.4%) cases proved to be false positives: trisomies 21 (n = 2), 18 (n = 1) and 13 (n = 2). Estimated reduction in invasive testing was 62%.
  
  
  CONCLUSIONS
  Introduction of NIPT in the Dutch National healthcare-funded Prenatal Screening Program resulted in high uptake and a vast reduction of invasive testing. Our study supports offering NIPT to pregnant women at increased risk for fetal trisomy. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Oepkes
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: G C Lieve
authors.initials: GC
authors.lastname: Page-Christiaens
authors.affiliation: Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Bax
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mireille N
authors.initials: MN
authors.lastname: Bekker
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Catia M
authors.initials: CM
authors.lastname: Bilardo
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elles M J
authors.initials: EM
authors.lastname: Boon
authors.affiliation: Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: G Heleen
authors.initials: GH
authors.lastname: Schuring-Blom
authors.affiliation: Department of Obstetrics and Gynaecology, Maastricht UMC+, Maastricht, The Netherlands.
authors.forename: Audrey B C
authors.initials: AB
authors.lastname: Coumans
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Brigitte H
authors.initials: BH
authors.lastname: Faas
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Robert-Jan H
authors.initials: RH
authors.lastname: Galjaard
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Attie T
authors.initials: AT
authors.lastname: Go
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lidewij
authors.initials: L
authors.lastname: Henneman
authors.affiliation: Department of Clinical Genetics, Maastricht UMC+, Maastricht, The Netherlands.
authors.forename: Merryn V E
authors.initials: MV
authors.lastname: Macville
authors.affiliation: Department of Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Pajkrt
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Ron F
authors.initials: RF
authors.lastname: Suijkerbuijk
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Huijsdens-van Amsterdam
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Van Opstal
authors.affiliation: Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E J Joanne
authors.initials: EJ
authors.lastname: Verweij
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Weiss
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
mesh_terms: D000328:Adult; D025063:Chromosome Disorders / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004247:DNA / Q000097:blood*; D004314:Down Syndrome / Q000175:diagnosis; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005500:Follow-Up Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009426:Netherlands; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D017422:Sequence Analysis, DNA / Q000379:methods*; D013997:Time Factors; D014314:Trisomy / Q000175:diagnosis; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome; D016216:Ultrasonography, Prenatal
chemical_list: D004247:DNA