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
- 2
Shuttleworth G E.
Mongolian imbecility.
BMJ.
1909;
2
661-665
- 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
- 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
- 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
- 6
Jack B W, Empkie T M, Kates R B.
Routine obstetric ultrasound.
Am Fam Physician.
1987;
35
173-182
- 7
Steele M W, Breg W R.
Chromosome analysis of human amniotic-fluid cells.
Lancet.
1966;
1(7434)
383-385
- 8
Valenti C, Schutta E J, Kehaty T.
Prenatal diagnosis of Down's syndrome.
Lancet.
1968;
2
220
- 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
- 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
- 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
- 12
Sundberg K, Jorgensen F S, Tabor A, Bang J.
Experience with early amniocentesis.
J Perinat Med.
1995;
23
149-158
- 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
- 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
- 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
- 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
- 17
Cuckle H.
Integrating antenatal Down's syndrome screening.
Curr Opin Obstet Gynecol.
2001;
13
175-181
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 28
Cuckle H S, van Lith J M.
Appropriate biochemical parameters in first-trimester screening for Down syndrome.
Prenat Diagn.
1999;
19
505-512
- 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
- 30
Cuckle H.
Time for total shift to first-trimester screening for Down's syndrome.
Lancet.
2001;
358
1658-1659
- 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
- 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
- 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
- 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
- 35
Cuckle H S.
Growing complexity in the choice of Down's syndrome screening policy.
Ultrasound Obstet Gynecol.
2002;
19
323-326
- 36
Shipp T D, Benacerraf B R.
Second trimester ultrasound screening for chromosomal abnormalities.
Prenat Diagn.
2002;
22
296-307
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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
