NIPT og prænatal screening

NIPT og prænatal screening Møderække med SST: DFMS, DSMG, DSOG, (DSKB) 13. Januar, 24. Februar, 31. Marts, 15. Maj 2014 Off. Sygehuse: Roskilde Ålborg Alle? Private klinikker: Mange! 2 1

Abnorme karyotyper 1,122 (11.0) e karyotyper Kan diagnosticeres med NIPT: 72.6 Trisomi 21 500 Trisomi 18/13 189 Sex aneuploidi 126 Kan ikke diagnosticeres med NIPT: 27.4 Balancerede translokationer 45 Med høj risiko for fænotype: 262 Ubalancerede translokationer, andre ubalancerede re-arrangementer, deletioner, triploidi, andre autosomale trisomier 2

Risiko for atypisk karyotype Risikofaktor Risiko øges ved Cut-off Mors alder é Alder 45 År NF é NF 3.5 mm Dobbelt test MoM er é fβ-hcg ê fβ-hcg and PAPP- A 5 MoM 0.2 MoM T21 Risiko é T21 Risiko 1:150 Ingen risko faktor: (97): Prævalens <0.1 En eller flere risko faktorer (3) Prævalens 1.6 Prænatal array AJOG 2014-early view UOG 2014-accepted 3

NOT SO FAST! WHAT ARE WE MISSING WITH NIPS? Mark I. Evans, MD Professor Mt. Sinai School of Medicine New York NIPS roll out: RIGHT ANSWERS TO WRONG QUESTIONS Good News: excellent screen NIPS > combined DS screen Limits # of cvs/amnio needed Expanding utilization to hesitant patients Still Gallup poll not election results 99 sensitivity isn t 99 PPV Patent litigation; everybody suing everybody 1/3 rd of abns diff than screen + Bad news: only a screen Expensive (but decreasing) High no call rate. (coming down) Many clinicians abandoning NT thereby missing GA and placentation Twins/zygosity Anomalies Misses all the other chromosome alities MPSS expanding In USA, hyped marketing replaces amnio CGH has moved the goal posts further back Still a role for biochemistry 4

Test strategi CVS v/t21 risiko >1:300 CV S NIP T T21 N=125 Detektions rate () T13/T18 N=189 Køns kromos om N=126 Atypisk N=66 Alle e N=269 4.1 0 87.2 71,4 78,6 32.2 70.0 Risiko faktorer: Alder 45år, NF 3.5 mm, fβ-hcg 5 MoM, fβ-hcg eller PAPP-A < 0.2 MoM Data er pr år for perioden 2008-2011 Test strategi CVS v/t21 risiko >1:300 NIPT til alle (n=48.410) CV S NIP T T21 N=125 Detektions rate () T13/T18 N=189 Køns kromos om N=126 Atypisk N=66 Alle e N=269 4.1 0 87.2 71,4 78,6 32.2 70.0 0 100 100 100 100 0 75.7 Risiko faktorer: Alder 45år, NF 3.5 mm, fβ-hcg 5 MoM, fβ-hcg eller PAPP-A < 0.2 MoM Data er pr år for perioden 2008-2011 5

Test strategi CVS v/t21 risiko >1:300 NIPT til alle (n=48.410) CVS >1:300+risiko faktor CV S NIP T T21 N=125 Detektions rate () T13/T18 N=189 Køns kromos om N=126 Atypisk N=66 Alle e N=269 4.1 0 87.2 71,4 78,6 32.2 70.0 0 100 100 100 100 0 75.7 4,7 0 87,6 79,9 81,0 37,8 73,4 Risiko faktorer: Alder 45år, NF 3.5 mm, fβ-hcg 5 MoM, fβ-hcg eller PAPP-A < 0.2 MoM Data er pr år for perioden 2008-2011 Test strategi CVS v/t21 risiko >1:300 NIPT til alle (n=48.410) CVS >1:300+risiko faktor CVS >1:300+risiko faktor NIPT 1:300-1:1000 CV S NIP T T21 N=125 Detektions rate () T13/T18 N=189 Køns kromos om N=126 Atypisk N=66 Alle e N=269 4.1 0 87.2 71,4 78,6 32.2 70.0 0 100 100 100 100 0 75.7 4,7 0 87,6 79,9 81,0 37,8 73,4 4,7 5,6 93,6 84,7 82,5 37,8 77,2 Risiko faktorer: Alder 45år, NF 3.5 mm, fβ-hcg 5 MoM, fβ-hcg eller PAPP-A < 0.2 MoM Data er pr år for perioden 2008-2011 6

Test strategi CVS v/t21 risiko >1:300 NIPT til alle (n=48.410) CVS >1:300+risiko faktor CVS >1:250+risiko faktor NIPT 1:250-1:500 CVS >1:300+risiko faktor NIPT 1:300-1:1000 CV S NIP T T21 N=125 Detektions rate () T13/T18 N=189 Køns kromos om N=126 Atypisk N=66 Alle e N=269 4.1 0 87.2 71,4 78,6 32.2 70.0 0 100 100 100 100 0 75.7 4,7 0 87,6 79,9 81,0 37,8 73,4 4,3 2,1 91,2 82,0 81,7 37,4 75,4 4,7 5,6 93,6 84,7 82,5 37,8 77,2 Risiko faktorer: Alder 45år, NF 3.5 mm, fβ-hcg 5 MoM, fβ-hcg eller PAPP-A < 0.2 MoM Data er pr år for perioden 2008-2011 Detektionsrate og cut-off 7

Økonomi Lab + rådgivning/år CVS cutoff NIPT cutoff Array andel Pris total N case Pris/case 1:300gl Ingen 30 13.029.000 189 69.121 Kun NIPT Alle 0 194.811.625 204 956.131 1:300ny Ingen 100 21.236.000 >199 106.184 1:250ny 1:500 100 23.485.425 >203 115.692 1:300ny 1:1.000 100 32.168.000 >208 154.839 1:300gl = den algoritme vi bruger i dag, med T21 cut-off for CVS 1:300 1:250/300ny = Ny algoritme: CVS tilbydes til: Alder >=45 år og/eller NF>=3,5 mm, og/eller skæv biokemi og/eller T21 cut-off 1:250/300 Forudsætninger/analysepris: NIPT: 4.000,- array-cgh: 9.300,- Konventionel karyotype: 5.300,- DFMS-DSOG-DSMG forslag Fortsat tilbyde kombineret 1. trim screening Fortsat tilbyde CVS ved risiko >1:300 (højrisiko) Tilbyde NIPT til dem med en risiko mellem 1:300 og 1:1.000 (mellemrisiko) 8

Vigtig pointe For den enkelte kvinde vil array-cgh altid give mere klart diagnostisk information end NIPT Men hvis man tilbyder NIPT til mange flere, kan det set fra samfundet give en høj samlet detektionsrate i populationen. Selvom teknikken overser ¼ af de e kromosomfejl Er CVS nu også så farligt? 9

Risk of fetal loss from invasive testing - a national cohort study CB. Wulff, S. Ball, L. Rode, CK. Ekelund, OB. Petersen, A. Tabor Objective To assess the risk of fetal loss following first trimester risk assessment with special reference to invasive testing after adjusting for maternal characteristics and first trimester findings Material and Methods Singleton pregnancies First trimester screening 1 January 2008-31 December 2010 Data retrieved from the Danish National Fetal Medicine Database Population: 144,187 (99.2) Live births 761 (0.5) Miscarriages (fetal loss before 22 wks of gestation) 444 (0.3) Stillbirths (fetal loss after 22 wks of gestation) Excluded: 2753 (1.9) pregnancies because of unknown outcome, termination or pre or postnatal chromosomal alities 1 Center of Fetal Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark 2 Center for Biostatistics and Bioinformatics,Plymouth University, United Kingdom. 3 Fetal Medicine Unit, Aarhus University Hospital, Denmark Results Risk of fetal loss from invasive testing Invasive test GA / weeks (median) Adjusted OR for fetal loss from invasive testing CVS 3.1 13 AC 1.1 17 Rate of fetal loss OR 0.8 (95 CI 0.5-1.1) OR 1.0 (95 CI 0.6-1.7) 2.0 OR 1.2 (95 0.7-2.0) 0.5 1.2 1.0 0.3 0.4 OR 6.1 (95 CI 4.2-9.1) Miscarriage Stillbirth no invasive test CVS AC Adjusted for maternal characteristics, method of conception, obstetric history and first trimester findings Marbella 2013 10

Risk of fetal loss from invasive testing Results Invasive test GA / weeks (median) Adjusted OR for fetal loss from invasive testing CVS 3.1 13 AC 1.1 17 Rate of fetal loss OR 0.8 (95 CI 0.5-1.1) OR 1.0 (95 CI 0.6-1.7) 2.0 OR 1.2 (95 0.7-2.0) 0.5 1.2 1.0 0.3 0.4 OR 6.1 (95 CI 4.2-9.1) Miscarriage Stillbirth no invasive test CVS AC Adjusted for maternal characteristics, method of conception, obstetric history and first trimester findings Marbella 2013 11

Risk of fetal loss from invasive testing Results Invasive test CVS 3.1 13 AC 1.1 17 Adjusted OR for fetal loss from invasive testing GA / weeks (median) OR 0.8 (95 CI 0.5-1.1) OR 1.0 (95 CI 0.6-1.7) Rate of fetal loss OR 1.2 (95 0.7-2.0) 2.0 1.2 OR 6.1 (95 CI 4.2-9.1) 1.0 0.5 Miscarriage no invasive test 0.3 0.4 Stillbirth CVS AC Adjusted for maternal characteristics, method of conception, obstetric history and first trimester findings Marbella 2013 The Danish Fetal Medicine Study Group: Karin Sundberg, Finn Stener Jørgensen, Torben Larsen, Annette Wind Olesen, Lillian Skibsted, Eva Hoseth, Marianne Christiansen, Lene Sperling, Helle Zingenberg, AnneCathrine Shalmi, Hanne Søndergaard Jensen, Richard Farlie, Marianne Østergaard, Mette Holm Ibsen Fra Vancouver Airport The Danish Clinical Genetics Study Group: Peter K A Jensen, Christina Fagerberg, Susanne Timshel, Susanne Kjærgaard, Anders Bojesen, Michael Bjørn Petersen TAK 12