Der combined test im ersten Schwangerschaftstrimenon bei 3316 nicht selektierten Schwangeren zur Diagnostik des M. Down[1]

Zusammenfassung

Hintergrund Die hohe pränatale Entdeckungsrate (ER) des Down-Syndroms, die durch die Messung der Nackentransparenz (NT) in der Frühschwangerschaft erzielt wird, wird durch die Kombination mit Plazentahormonen (PAPP-A, fβHCG) und dem mütterlichen Alter noch gesteigert („combined-test”). Wie hoch ist die ER des „combined-tests” in einem Kollektiv unselektierter, nicht zugewiesener Schwangerer bei einer Falschpositivenrate (FPR) von ca. 5 %.

Material und Methode Bei allen Frauen mit Einlingsschwangerschaften wurde im Zeitraum vom 1. 12. 97 - 31. 12. 99 zwischen der 10. und 13. Schwangerschaftswoche (Scheitelsteißlänge 3570 mm) die NT, das PAPP-A und das fβHCG gemessen. Die Berechnung des individuellen Down-Risikos erfolgte mit dem Programm Alpha, Version 5aa (Logical medical systems, London).

Ergebnisse Der Test wurde bei 3316 Schwangeren durchgeführt. 9 der 10 Downschwangerschaften, die in diesem Zeitraum auftraten, konnten damit entdeckt werden. 137 Frauen waren testpositiv, hatten aber keine Downschwangerschaft (FPR von 4,1 %).

Schlussfolgerungen Der „combined-test” ist auch in einem „low-risk”-Kollektiv ein ausgezeichneter Test zur Entdeckung des M. Down.

Diskussion Das ständig steigende Durchschnittsalter der Schwangeren würde bei Anwendung der Altersamniozentese die ER zwar moderat anheben, das aber zum Preis stark vermehrter Eingriffe und Fehlgeburten. Mit dem „combined-test” kann man die ER des M. Down bei viel geringeren FPR (ca. 5 %) weitaus deutlicher steigern.

The high detection rate (DR) for Down syndrome pregnancies which can be achieved by measuring fetal nuchal translucency (NT) early in pregnancy can be improved by combining it with placental hormones (PAPP-A, fβhCG) and maternal age (“combined test”). In this study we wanted to assess the DR using the “combined test” in an unselected population of self-referred pregnant women at a false positive rate (FPR) of about 5 %.

Materials and Methods NT, PAPP-A, fβhCG and maternal age were measured in all women with singleton pregnancies who booked for delivery in our hospital from 1. 12. 97 to 31. 12. 99 and who were between 10 and 13 completed weeks of gestation (crown-rump-length 35 - 70 mm). Calculation of the specific Down risk was done with the computer program Alpha, Version 5aa (Logical medical systems, London).

Results A total of 3316 women were tested. Out of 10 Down pregnancies, which occurred in this period of time 9 could be detected with the test. 137 women had a positive test result but a non-Down pregnancy (FPR 4.1 %).

Conclusions The combined test is an excellent test for the detection of Down syndrome pregnancies in a low-risk population.

Discussion The constant increase in maternal age at the time of delivery can also lead to an improved DR if a simple age dependant protocol for Down-detection is used, but only at the price of a much higher number of amniocenteses and subsequent abortions. The DR for Down syndrome can be increased much more markedly using the “combined test” at a much lower FPR (∼ 5 %).

Erstes Trimenon - Down Screening - combined test

First trimenon - down screening - combined test

Literatur

1 Eingang: 16. 8. 2000
Angenommen nach Revision: 23. 11. 2000

• 01 Nicolaides  K H, Azar  G, Mansur  C, Marks  K. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.  BMJ. 1992;  304 867-869
• 02 Schulte-Vallentin  M, et al. Non echogenic nuchal oedema as a marker in trisomy 21 screening.  Lancet. 1992;  339 1053
• 03 Hafner  E, Schuchter  K, Philipp  K. Screening for chromosomal abnormalities in an unselected population by fetal nuchal translucency.  Ultrasound Obstet Gynecol. 1995;  6 330-333
• 04 Szabo  J, Gellen  J, Szemere  G. First-trimester ultrasound screening for fetal aneuploidies in women over 35 and under 35 years of age.  Ultrasound Obstet Gynecol. 1995;  5 161-163
• 05 Brambati  B, Cislaghi  C, Tului  L, Alberti  E, Amidami  M, Colombo  U, Zuliani  G. First trimester Down's syndrome screening using nuchal translucency: a prospective study in patients undergoing chorionic villus sampling.  Ultrasound Obstet Gynecol. 1995;  5 9-14
• 06 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
• 07 Wald  N J, Kenard  A, Hackshaw  A K. First trimester serum screening for Down's syndrome.  Prenat Diagn. 1995;  15 1227-1240
• 08 Haddow  J E, Palomaki  G E, Knight  G J, Williams  J, Miller  W A, Johnson  A. Screening of maternal serum for fetal Down's syndrome in the first trimester.  N Engl J Med. 1998;  338 955-961
• 09 Hackshaw  A K, et al. Down's syndrome screening with nuchal translucency.  Lancet. 1996;  348 1740
• 10 Wald  N J, Hackshaw  A K. Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome.  Prenat Diagn. 1997;  17 821-829
• 11 Orlandi  F, Damiani  G, Hallahan  T W, Krantz  D A, Macri  J N. First-trimester screening for fetal aneuploidy: biochemistry and nuchal translucency.  Ultrasound ObstetGynecol. 1997;  10 381-386
• 12 Biagiotti  R, Brizi  L, Periti  E, d'Agata  A, Vanz  E, Cariati  E. First trimester screening for Down's syndrome using maternal serum PAPP-A and free beta-hCG in combination with fetal nuchal translucency thickness.  Br J Obstet Gynaecol. 1998;  105 917-920
• 13 Spencer  K, Souter  V, Tul  N, Snijders  R, Nicolaides  K H. A screening program for trisomy 21 at 10 - 14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A.  Ultrasound Obstet Gynecol. 1999;  13 231
• 14 De Biasio  P, Siccardi  M, Volpe  G, Famularo  L, Santi  F, Canini  S. First-trimester screening for Down syndrome using nuchal translucency measurement with free beta-hCG and PAPP-A between 10 and 13 weeks of pregnancy - the combined test.  Prenat Diagn. 1999;  19 360-363
• 15 De Graaf  I M, Pajkrt  E, Bilardo  C M, Leschot  N J, Cuckle  H S, van Lith  J M. Early pregnancy screening for aneuploidy with serum markers and nuchal translucency.  Prenat Diagn. 1999;  19 458-462
• 16 Tsukerman  G L, Gusina  N B, Cuckle  H S. Maternal serum screening for Down syndrome in the first trimester experience from Belarus.  Prenat Diagn. 1999;  19 499-504
• 17 Cuckle  H S, van Lith  J M. Appropriate biochemical parameters in first-trimester screening for Down syndrome.  Prenat Diagn. 1999;  19 505-512
• 18 Schuchter  K, Wald  N, Hackshaw  A K, Hafner  E, Liebhart  E. The distribution of nuchal translucency at 10 - 13 weeks of pregnancy.  Prenat Diagn. 1998;  18 281-286
• 19 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
• 20 Macintosh  M C, Wald  N J, Chard  T, Hansen  J, Mikkelsen  M, Therkelsen  A J, Petersen  G B, Lundsteen  C. The selective miscarriage of Down's syndrome from 10 weeks of pregnancy.  Br J Obstet Gynaecol. 1996;  103 117-123
• 21 Hafner  E, Schuchter  K, Philipp  K. Screening for chromosomal abnormalities in an unselected population by fetal nuchal translucency.  Ultrasound Obstet Gynecol. 1995;  6 330-333
• 22 Hafner  E, Schuchter  K, Liebhart  E, Philipp  K. Results of routine fetal nuchal translucency measurement at weeks 10 - 13 in 4233 unselected pregnant women.  Prenat Diagn. 1998;  18 29-34
• 23 Wald  N J, George  L, Smith  D, Densem  J W, Petterson  K. Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group.  Br J Obstet Gynaecol. 1996;  103 407-412