Download PDF
Geburtshilfe Frauenheilkd 2002; 62(9): 843-848
DOI: 10.1055/s-2002-33894
Übersicht

Georg Thieme Verlag Stuttgart · New York

Down-Syndrom-Screening im ersten Trimenon

Screening for Down's Syndrome in the First Trimester of PregnancyE. Krampl, D. Wertaschnigg, P. Husslein
  • Abteilung für Geburtshilfe, Universitätsklinik für Frauenheilkunde, Wien, Österreich
Further Information

Publication History

Eingang Manuskript: 3. Juni 2002 Eingang revidiertes Manuskript: 28. Juli 2002

Akzeptiert: 31. Juli 2002

Publication Date:
06 September 2002 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Down-Syndrom ist die Ursache für ungefähr ein Drittel aller geistigen Behinderungen. Mit einer Prävalenz von 0,2 % aller Schwangerschaften und der Möglichkeit einer sicheren pränatalen Diagnostik mittels Chorionzottenbiopsie oder Amniozentese ist heutzutage jeder Gynäkologe während der Schwangerenbetreuung zur Beratung über Chromosomenanomalien aufgefordert. Die Basis bildet das altersentsprechende Risiko, und ein Hinzuziehen der quantifizierbaren fetalen Hinweiszeichen individualisiert die Risikoberechnung und verbessert die Entdeckungsrate für Down-Syndrom. Diese liegt bei einer Falsch-positiv-Rate von 5 % bei reinem Alters-Screening (Cut-off in Deutschland/Österreich 37 Jahre) bei 30 %. Modifiziert man das Risiko durch die Messung der Nackentransparenz und der Serumkonzentrationen von freiem β-human chorionic gonadotrophin (hCG) und pregnancy associated plasma protein-A (PAPP-A), steigt die Entdeckungsrate auf rund 90 %. Diese Information sollte heute jeder Schwangeren zugänglich gemacht werden.

Abstract

Down's syndrome accounts for roughly one third of all causes of mental handicap. It has a prevalence of 0.2 % of all pregnancies and, with the availability of prenatal diagnosis by chorionic villus sampling or amniocentesis, every obstetrician faces the challenge of counseling his patients about chromosomal abnormalities. Combining quantifiable fetal markers with the maternal age-related risk individualises the risk calculation and improves the detection rate of Down's syndrome. Thus, at a 5 % false-positive rate, the detection rate is 30 % for age-based screening (age cut-off of 37 years in Germany/Austria), and if the nuchal translucency measurement and maternal serum concentrations of free b-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein A (PAPP-A) are taken into account, the detection rate increases to about 90 %. This information should be provided to every pregnant woman.

Literatur

  • 1 Down L J. Observations on an ethnic classification of idiots. Clinical Lectures and Reports. London Hospital 1866: 259-262
    Search in Google Scholar
  • 2 Shuttleworth G E. Mongolian imbecility.  BMJ. 1909;  2 661-665
    PubMedSearch in Google Scholar
  • 3 Snijders R J, Sundberg K, Holzgreve W, Henry G, Nicolaides K H. Maternal age- and gestation-specific risk for trisomy 21.  Ultrasound Obstet Gynecol. 1999;  13 167-170
    CrossrefPubMedSearch in Google Scholar
  • 4 Hagard S, Carter F A. Preventing the birth of infants with Down's syndrome: a cost-benefit analysis.  Br Med J. 1976;  1 753-756
    PubMedSearch in Google Scholar
  • 5 Jabeen T, Cannon B, Hogan J, Crowley M, Devereux C, Fanning L, Kenny-Walsh E, Shanahan F, Whelton M J. Pregnancy and pregnancy outcome in hepatitis C type 1 b.  Qjm. 2000;  93 597-601
    CrossrefPubMedSearch in Google Scholar
  • 6 Jack B W, Empkie T M, Kates R B. Routine obstetric ultrasound.  Am Fam Physician. 1987;  35 173-182
    PubMedSearch in Google Scholar
  • 7 Steele M W, Breg W R. Chromosome analysis of human amniotic-fluid cells.  Lancet. 1966;  1(7434) 383-385
    PubMedSearch in Google Scholar
  • 8 Valenti C, Schutta E J, Kehaty T. Prenatal diagnosis of Down's syndrome.  Lancet. 1968;  2 220
    PubMedSearch in Google Scholar
  • 9 Tabor A, Philip J, Madsen M, Bang J, Obel E B, Norgaard-Pedersen B. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women.  Lancet. 1986;  1 1287-1293
    PubMedSearch in Google Scholar
  • 10 The Canadian Early and Mid-trimester Amniocentesis Trial Group ( CEMAT). Randomised trial to assess safety and fetal outcome of early and midtrimester amniocentesis.  Lancet. 1998;  351 242-247
    CrossrefPubMedSearch in Google Scholar
  • 11 Nicolaides K, Brizot Md L, Patel F, Snijders R. Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10 - 13 weeks' gestation [published erratum appears in Lancet 1994; 17: 344 (8925): 830] [see comments].  Lancet. 1994;  344 435-439
    CrossrefPubMedSearch in Google Scholar
  • 12 Sundberg K, Jorgensen F S, Tabor A, Bang J. Experience with early amniocentesis.  J Perinat Med. 1995;  23 149-158
    PubMedSearch in Google Scholar
  • 13 Canadian Collaborative CVS-Amniocentesis Clinical Trial Group . Multicentre randomised clinical trial of chorion villus sampling and amniocentesis. First report.  Lancet. 1989;  1 1-6
    PubMedSearch in Google Scholar
  • 14 Smidt-Jensen S, Permin M, Philip J, Lundsteen C, Zachary J M, Fowler S E, Gruning K. Randomised comparison of amniocentesis and transabdominal and transcervical chorionic villus sampling.  Lancet. 1992;  340 1237-1244
    CrossrefPubMedSearch in Google Scholar
  • 15 Ammala P, Hiilesmaa V K, Liukkonen S, Saisto T, Teramo K, von Koskull H. Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis.  Prenat Diagn. 1993;  13 919-927
    PubMedSearch in Google Scholar
  • 16 Snijders R J, Noble P, Sebire N, Souka A, Nicolaides K H. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10 - 14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group.  Lancet. 1998;  352 343-346
    CrossrefPubMedSearch in Google Scholar
  • 17 Cuckle H. Integrating antenatal Down's syndrome screening.  Curr Opin Obstet Gynecol. 2001;  13 175-181
    CrossrefPubMedSearch in Google Scholar
  • 18 Matias A, Gomes C, Flack N, Montenegro N, Nicolaides K H. Screening for chromosomal abnormalities at 10 - 14 weeks: the role of ductus venosus blood flow.  Ultrasound Obstet Gynecol. 1998;  12 380-384
    CrossrefPubMedSearch in Google Scholar
  • 19 Bilardo C M, Muller M A, Zikulnig L, Schipper M, Hecher K. Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome.  Ultrasound Obstet Gynecol. 2001;  17 288-294
    CrossrefPubMedSearch in Google Scholar
  • 20 Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11 - 14 weeks of gestation: an observational study.  Lancet. 2001;  358 1665-1667
    CrossrefPubMedSearch in Google Scholar
  • 21 Souka A P, Krampl E, Bakalis S, Heath V, Nicolaides K H. Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester.  Ultrasound Obstet Gynecol. 2001;  18 9-17
    PubMedSearch in Google Scholar
  • 22 Hyett J A, Brizot M L, Von Kaisenberg C S, McKie A T, Farzaneh F, Nicolaides K H. Cardiac gene expression of atrial natriuretic peptide and brain natriuretic peptide in trisomic fetuses.  Obstet Gynecol. 1996;  87 506-510
    PubMedSearch in Google Scholar
  • 23 Hyett J, Moscoso G, Nicolaides K. Increased nuchal translucency in trisomy 21 fetuses: relationship to narrowing of the aortic isthmus.  Hum Reprod. 1995;  10 3049-3051
    PubMedSearch in Google Scholar
  • 24 von Kaisenberg C S, Nicolaides K H, Brand-Saberi B. Lymphatic vessel hypoplasia in fetuses with Turner syndrome.  Hum Reprod. 1999;  14 823-826
    CrossrefPubMedSearch in Google Scholar
  • 25 Sebire N J, Snijders R J, Davenport M, Greenough A, Nicolaides K H. Fetal nuchal translucency thickness at 10 - 14 weeks' gestation and congenital diaphragmatic hernia.  Obstet Gynecol. 1997;  90 943-946
    CrossrefPubMedSearch in Google Scholar
  • 26 Souka A P, Snijders R J, Novakov A, Soares W, Nicolaides K H. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10 - 14 weeks of gestation.  Ultrasound Obstet Gynecol. 1998;  11 391-400
    CrossrefPubMedSearch in Google Scholar
  • 27 von Kaisenberg C S, Krenn V, Ludwig M, Nicolaides K H, Brand-Saberi B. Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12 - 18 weeks and in a trisomy 16 mouse.  Anat Embryol (Berl). 1998;  197 105-124
    CrossrefPubMedSearch in Google Scholar
  • 28 Cuckle H S, van Lith J M. Appropriate biochemical parameters in first-trimester screening for Down syndrome.  Prenat Diagn. 1999;  19 505-512
    CrossrefPubMedSearch in Google Scholar
  • 29 Knofler M. What factors regulate HCG production in Down's syndrome pregnancies? Regulation of HCG during normal gestation and in pregnancies affected by Down's syndrome.  Mol Hum Reprod. 1999;  5 895-897
    CrossrefPubMedSearch in Google Scholar
  • 30 Cuckle H. Time for total shift to first-trimester screening for Down's syndrome.  Lancet. 2001;  358 1658-1659
    CrossrefPubMedSearch in Google Scholar
  • 31 Hackshaw A K, Wald N J. Assessment of the value of reporting partial screening results in prenatal screening for Down syndrome.  Prenat Diagn. 2001;  21 737-740
    CrossrefPubMedSearch in Google Scholar
  • 32 Spencer K, Spencer C E, Power M, Moakes A, Nicolaides K H. One stop clinic for assessment of risk for fetal anomalies: a report of the first year of prospective screening for chromosomal anomalies in the first trimester.  Br J Obstet Gynaecol. 2000;  107 1271-1275
    PubMedSearch in Google Scholar
  • 33 Spencer K. Age related detection and false positive rates when screening for Down's syndrome in the first trimester using fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A.  Br J Obstet Gynaecol. 2001;  108 1043-1046
    CrossrefPubMedSearch in Google Scholar
  • 34 Spencer K. Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry.  Prenat Diagn. 2002;  22 244-246
    CrossrefPubMedSearch in Google Scholar
  • 35 Cuckle H S. Growing complexity in the choice of Down's syndrome screening policy.  Ultrasound Obstet Gynecol. 2002;  19 323-326
    PubMedSearch in Google Scholar
  • 36 Shipp T D, Benacerraf B R. Second trimester ultrasound screening for chromosomal abnormalities.  Prenat Diagn. 2002;  22 296-307
    CrossrefPubMedSearch in Google Scholar
  • 37 Thilaganathan B, Olawaiye A, Sairam S, Harrington K. Isolated fetal echogenic intracardiac foci or golf balls: is karyotyping for Down's syndrome indicated?.  Br J Obstet Gynaecol. 1999;  106 1294-1297
    PubMedSearch in Google Scholar
  • 38 Nicolaides K H, Heath V, Liao A W. The 11 - 14 week scan.  Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;  14 581-594
    PubMedSearch in Google Scholar
  • 39 Theodoropoulos P, Lolis D, Papageorgiou C, Papaioannou S, Plachouras N, Makrydimas G. Evaluation of first-trimester screening by fetal nuchal translucency and maternal age.  Prenat Diagn. 1998;  18 133-137
    CrossrefPubMedSearch in Google Scholar
  • 40 Schwarzler P, Carvalho J S, Senat M V, Masroor T, Campbell S, Ville Y. Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at 10 - 14 weeks of gestation as part of routine antenatal care in an unselected population.  Br J Obstet Gynaecol. 1999;  106 1029-1034
    PubMedSearch in Google Scholar
  • 41 Gasiorek-Wiens A, Tercanli S, Kozlowski P, Kossakiewicz A, Minderer S, Meyberg H. et al . Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland.  Ultrasound Obstet Gynecol. 2001;  18 645-648
    PubMedSearch in Google Scholar
  • 42 Zoppi M A, Ibba R M, Putzolu M, Floris M, Monni G. Assessment of risk for chromosomal abnormalities at 10 - 14 weeks of gestation by nuchal translucency and maternal age in 5210 fetuses at a single centre.  Fetal Diagn Ther. 2000;  15 170-173
    CrossrefPubMedSearch in Google Scholar
  • 43 Brizot M L, Carvalho M H, Liao A W, Reis N S, Armbruster-Moraes E, Zugaib M. First-trimester screening for chromosomal abnormalities by fetal nuchal translucency in a Brazilian population.  Ultrasound Obstet Gynecol. 2001;  18 652-655
    PubMedSearch in Google Scholar
  • 44 Tercanli S, Holzgreve W, Batukan C, Gerber A, Ermis H, Miny P. Screening for aneuploidy by first trimester nuchal translucency measurement: results from a prospective trial including 1980 cases in a single center in Switzerland.  Ultraschall Med. 2002;  23 22-26
    Thieme ConnectPubMedSearch in Google Scholar
  • 45 Krantz D A, Hallahan T W, Orlandi F, Buchanan P, Larsen J W, Macri J N. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency.  Obstet Gynecol. 2000;  96 207-213
    CrossrefPubMedSearch in Google Scholar
  • 46 Schuchter K, Hafner E, Stangl G, Metzenbauer M, Hofinger D, Philipp K. The first trimester “combined test” for the detection of Down syndrome pregnancies in 4939 unselected pregnancies.  Prenat Diagn. 2002;  22 211-215
    CrossrefPubMedSearch in Google Scholar

Univ.-Doz. Dr. Elisabeth Krampl

Abteilung für Geburtshilfe, Universitätsklinik für Frauenheilkunde

Währinger Gürtel 18 - 20

A-1090 Wien

Österreich

Email: elisabeth.krampl@akh-wien.ac.at