PDF herunterladen
Geburtshilfe Frauenheilkd 2012; 72(11): 998-1003
DOI: 10.1055/s-0032-1327960
Review
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Assessment of Foetal DNA in Maternal Blood – A Useful Tool in the Hands of Prenatal Specialists

Bestimmung der fetalen DNA im mütterlichen Blut – Sinnvoller Einsatz in der Hand des Pränatalmediziners
K. O. Kagan
1   Department of Obstetrics and Gynaecology, University of Tübingen
,
M. Hoopmann
1   Department of Obstetrics and Gynaecology, University of Tübingen
,
P. Kozlowski
2   praenatal.de, Praenatal-Medizin und Genetik Düsseldorf
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 19. September 2012
revised 19. Oktober 2012

accepted 21. Oktober 2012

Publikationsdatum:
12. Dezember 2012 (online)

Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Over the last few years, first trimester screening between 11+ and 13+ weeks of gestation has become one of the most important ultrasound examinations in pregnancy, as it allows physicians to predict several pregnancy complications including pre-eclampsia or pre-term birth. Screening for trisomies 21/18 and 13 using maternal and gestational age, foetal nuchal translucency, and maternal serum biochemistry was formerly the main reason for first trimester screening. However, today this is only one part of the overall examination. In the near future, the analysis of foetal DNA obtained from maternal blood will be used to supplement first trimester screening for aneuploidy or even replace current screening methods. In this review we show how prenatal medicine specialists can use foetal DNA analysis.

Zusammenfassung

Das Ersttrimesterscreening in der 11 + bis 13 + SSW hat sich in den vergangenen Jahren zu einer der zentralen Ultraschalluntersuchungen in der Schwangerschaft entwickelt, welche die Prädiktion zahlreicher Probleme in der Schwangerschaft, wie Präeklampsie oder Frühgeburtlichkeit, erlaubt. Die eigentliche Risikoberechnung für Trisomie 21/18 und 13, basierend auf dem mütterlichen Altersrisiko, der fetalen Nackentransparenz und der maternalen Serumbiochemie, stellt dabei nur einen der Schwerpunkte dar, der zukünftig durch die fetale DNA-Analyse aus mütterlichem Blut ergänzt bzw. abgelöst wird. In dieser Übersichtsarbeit wird der Einsatz der fetalen DNA-Analyse in der Hand des Pränatalmediziners beleuchtet.

Key words

foetal DNA - ultrasound - first trimester screening - trisomy

Schlüsselwörter

fetale DNA - Ultraschall - Ersttrimesterscreening - Trisomie

Supporting Information

 

  • Literatur

  • 1 Nicolaides KH. Turning the pyramid of prenatal care. Fetal Diagn Ther 2011; 29: 183-196
    CrossrefPubMedGoogle Scholar
  • 2 Bujold E, Roberge S, Lacasse Y et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116 (2 Pt 1) 402-414
    CrossrefPubMedGoogle Scholar
  • 3 Stumm M, Entezami M, Trunk N et al. Noninvasive prenatal detection of chromosomal aneuploidies using different next generation sequencing strategies and algorithms. Prenat Diagn 2012; 32: 569-577
    CrossrefPubMedGoogle Scholar
  • 4 Lo YM, Corbetta N, Chamberlain PF et al. Presence of fetal DNA in maternal plasma and serum. Lancet 1997; 350: 485-487
    CrossrefPubMedGoogle Scholar
  • 5 Chiu RWK, Lo YMD. Noninvasive prenatal diagnosis empowered by high-throughput sequencing. Prenat Diagn 2012; 32: 401-406
    CrossrefPubMedGoogle Scholar
  • 6 Ashoor G, Poon L, Syngelaki A et al. Fetal fraction in maternal plasma cell-free DNA at 11–13 weeksʼ gestation: effect of maternal and fetal factors. Fetal Diagn Ther 2012; 31: 237-243
    CrossrefPubMedGoogle Scholar
  • 7 Chiu RWK, Chan KCA, Gao Y et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci U S A 2008; 105: 20458-20463
    CrossrefPubMedGoogle Scholar
  • 8 Verweij EJ, van den Oever JME, de Boer MA et al. Diagnostic accuracy of noninvasive detection of fetal trisomy 21 in maternal blood: a systematic review. Fetal Diagn Ther 2012; 31: 81-86
    CrossrefPubMedGoogle Scholar
  • 9 Nicolaides KH, Syngelaki A, Ashoor G et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol 2012; 207: 374.e1-374.e6
    CrossrefPubMedGoogle Scholar
  • 10 Grati FR, Barlocco A, Grimi B et al. Chromosome abnormalities investigated by non-invasive prenatal testing account for approximately 50 % of fetal unbalances associated with relevant clinical phenotypes. Am J Med Genet 2010; 152: 1434-1442
    PubMedGoogle Scholar
  • 11 Wright D, Kagan KO, Molina FS et al. A mixture model of nuchal translucency thickness in screening for chromosomal defects. Ultrasound Obstet Gynecol 2008; 31: 376-383
    CrossrefPubMedGoogle Scholar
  • 12 Abele H, Wagner N, Hoopmann M et al. Effect of deviation from the mid-sagittal plane on the measurement of fetal nuchal translucency. Ultrasound Obstet Gynecol 2010; 35: 525-529
    CrossrefPubMedGoogle Scholar
  • 13 Syngelaki A, Chelemen T, Dagklis T et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11–13 weeks. Prenat Diagn 2011; 31: 90-102
    CrossrefPubMedGoogle Scholar
  • 14 Timmerman E, Pajkrt E, Maas SM et al. Enlarged nuchal translucency in chromosomally normal fetuses: strong association with orofacial clefts. Ultrasound Obstet Gynecol 2010; 36: 427-432
    CrossrefPubMedGoogle Scholar
  • 15 Kagan KO, Hoopmann M, Abele H et al. Zukünftige Entwicklung der Geburtsmedizin. Gynäkologe 2012; DOI: 10.1007/s00129-012-2964-2.
    PubMedGoogle Scholar
  • 16 Pereira S, Ganapathy R, Syngelaki A et al. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstet Gynecol 2011; 117: 1384-1391
    CrossrefPubMedGoogle Scholar
  • 17 Akolekar R, Syngelaki A, Sarquis R et al. Prediction of early, intermediate and late pre-eclampsia from maternal factors, biophysical and biochemical markers at 11-13 weeks. Prenat Diagn 2011; 31: 66-74
    CrossrefPubMedGoogle Scholar
  • 18 Greco E, Gupta R, Syngelaki A et al. First-trimester screening for spontaneous preterm delivery with maternal characteristics and cervical length. Fetal Diagn Ther 2012; 31: 154-161
    CrossrefPubMedGoogle Scholar
  • 19 Kozlowski P, Knippel A, Stressig R. Individual risk of fetal loss following routine second trimester amniocentesis: a controlled study of 20,460 cases. Ultraschall Med 2008; 29: 165-172
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 20 Tabor A, Alfirevic Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 2010; 27: 1-7
    CrossrefPubMedGoogle Scholar
  • 21 Kagan KO, Wright D, Baker A et al. Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008; 31: 618-624
    CrossrefPubMedGoogle Scholar
  • 22 Kagan KO, Valencia C, Livanos P et al. Tricuspid regurgitation in screening for trisomies 21, 18 and 13 and Turner syndrome at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 18-22
    CrossrefPubMedGoogle Scholar
  • 23 Maiz N, Valencia C, Kagan KO et al. Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 512-517
    CrossrefPubMedGoogle Scholar
  • 24 Kagan KO, Cicero S, Staboulidou I et al. Fetal nasal bone in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 259-264
    CrossrefPubMedGoogle Scholar
  • 25 Kagan KO, Etchegaray A, Zhou Y et al. Prospective validation of first-trimester combined screening for trisomy 21. Ultrasound Obstet Gynecol 2009; 34: 14-18
    PubMedGoogle Scholar
  • 26 Kagan KO, Wright D, Valencia C et al. Screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency, fetal heart rate, free-hCG and pregnancy-associated plasma protein-A. Hum Reprod 2008; 23: 1968-1975
    CrossrefPubMedGoogle Scholar
  • 27 Nicolaides KH. Screening for chromosomal defects. Ultrasound Obstet Gynecol 2003; 21: 313-321
    CrossrefPubMedGoogle Scholar
  • 28 Fan HC, Blumenfeld YJ, Chitkara U et al. Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood. Proc Natl Acad Sci U S A 2008; 105: 16266-16271
    CrossrefPubMedGoogle Scholar
  • 29 Sehnert AJ, Rhees B, Comstock D et al. Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood. Clin Chem 2011; 57: 1042-1049
    CrossrefPubMedGoogle Scholar
  • 30 Chiu RWK, Akolekar R, Zheng YWL et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011; 342: c7401
    CrossrefPubMedGoogle Scholar
  • 31 Ehrich M, Deciu C, Zwiefelhofer T et al. Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting. Am J Obstet Gynecol 2011; 204: 205.e1-205.e11
    PubMedGoogle Scholar
  • 32 Palomaki GE, Kloza EM, Lambert-Messerlian GM et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med 2011; 13: 913-920
    CrossrefPubMedGoogle Scholar
  • 33 Sparks AB, Wang ET, Struble CA et al. Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn 2012; 32: 3-9
    CrossrefPubMedGoogle Scholar
  • 34 Bianchi DW, Platt LD, Goldberg JD et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 2012; 119: 890-901
    CrossrefPubMedGoogle Scholar
  • 35 Sparks AB, Struble CA, Wang ET et al. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012; 206: 319.e1-319.e9
    CrossrefPubMedGoogle Scholar
  • 36 Wright D, Spencer K, Kagan KK et al. First-trimester combined screening for trisomy 21 at 7-14 weeksʼ gestation. Ultrasound Obstet Gynecol 2010; 36: 404-411
    CrossrefPubMedGoogle Scholar
  • 37 Cuckle HH, Benn PP, Wright DD. Down syndrome screening in the first and/or second trimester: model predicted performance using meta-analysis parameters. Semin Perinatol 2005; 29: 252-257
    CrossrefPubMedGoogle Scholar
  • 38 Hoopmann M, Abele H, Dufke A et al. Pränatale Diagnostik des Smith-Lemli-Opitz-Syndroms. Geburtshilfe Frauenheilkd 2011; 71: 128-131
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 39 Osmanağaoğlu MA, Caner Karahan S, Aran T et al. Predictive value of plasma total carnitine, arginine, asymmetric dimethylarginine and ischemia-modified albumin levels and their combined use in the early detection of preeclampsia. Geburtsh Frauenheilk 2011; 71: 773-778
    Artikel in Thieme ConnectPubMedGoogle Scholar