Analyse des Nackentransparenz (NT-)Screeningkonzepts an der Frauenklinik der MHH: Eine prospektive Follow-up-Studie

Zusammenfassung

Hintergrund und Fragestellung: Zur Berechnung der Eintrittswahrscheinlichkeit einer Trisomie 21 werden in Deutschland verschiedene, z. T. konkurrierende Suchstrategien angewandt. Ziel der vorliegenden Untersuchung war, die für die verschiedenen Methoden publizierten Leistungszahlen an einer Untersuchungsgruppe zu kontrollieren und damit den realen Stellenwert der einzelnen Methoden zu überprüfen.

Patientinnen und Methodik: An der Frauenklinik der MH Hannover wurden bei 744 Einlings-Schwangerschaften eine NT-Messung nach den Richtlinien der FMF London durchgeführt und zudem bei 590 der 744 Schwangeren die Konzentrationen von PAPP-A und freiem β-hCG in einem von der FMF London akkreditierten Labor bestimmt. Von allen 744 Patientinnen wurde das fetal outcome bestimmt. Darauf basierend wurden die Testleistungszahlen unter der hypothetischen Annahme, alle untersuchten Schwangeren hätten sich je einer der verschiedenen gängigen Suchstrategien unterworfen, ermittelt.

Ergebnisse: Das Alters-Screening erreichte die höchste Falsch-Positiv-Rate (25%), das kombinierte Screening nach Serummarkern und Alter die höchste Sensitivität (100%). Das kombinierte Screening nach Alter, NT-Wert und Serummarkern erreichte mit 97% die höchste Spezifität. Das kombinierte Screening nach NT-Wert und Alter erzielte die gleiche Sensitivität wie das Alters-Screening bei geringerer FPR als das kombinierte Screening nach Serummarkern und Alter. Es wurden bei 11% der Feten eine invasive Diagnostik durchgeführt. In 8% der Untersuchungen wurde ein auffälliger Karyotyp entdeckt.

Schlussfolgerung: Das Ersttrimester-Screening ermöglicht im Vergleich zur Altersindikation eine exaktere Definition der Risikogruppen für das Vorliegen numerischer Chromosomenstörungen. Damit ist die klinische Bedeutsamkeit der Untersuchung gerechtfertigt. Hierdurch werden insgesamt weniger Amniozentesen bei anteilig mehr jüngeren Schwangeren durchgeführt.

Abstract

Background: To date, various and partly competitive screening strategies for the risk calculation of trisomy 21 are applied in Germany. The aim of this study was to control the published test performance data of different methods in an unselected group of patients, thus allowing us to clearly assess the practical value of the respective methods.

Patients and Methods: At the MH Hannover, 744 women with a singleton pregnancy underwent an NT measurement according to the FMF guidelines. Additionally, 590 of these women had a PAPP-A and free ßHCG testing in a laboratory accredited by the FMF London. The fetal outcome of all 744 patients examined was assessed. Based on these data, test performance values were calculated for each test strategy under the hypothetical assumption that every women would have followed the same screening strategy.

Results: Age-related screening revealed to have the highest false-positive rate (25%). Age screening combined with serum markers showed to have the highest sensitivity (100%). Screening combining age, NT measurement and serum markers yielded the highest specificity (97%). Combined screening by NT and age achieved the same sensitivity as age-related screening with a markedly lower false-positive rate than screening combining age and serum markers. Invasive tests were performed in 11% of the patients. In 8% of these, a pathologic karyotype was detected.

Conclusions: In comparison to age-related screening, first trimester screening allows us to define groups at risk for trisomy 21 more clearly. This seems to justify the clinical importance of this search strategy, and accordingly, invasive procedures are done less frequently in a higher proportion of younger women.

Schlüsselwörter

Ersttrimester-Screening - Trisomie 21 - Nackentransparenz

Key words

First trimester screening - trisomy 21 - nuchal translucency

• Literatur

• 1 Schmidtke J. Vererbung und Ererbtes. Reinbeck bei Hamburg: Rowohlt Taschenbuch Verlag GmbH; 1997
• 2 Wald NJ, Cuckle HS. Recent advances in screening for neural tube defects and Down’s syndromeBallière’s. Clin Obstet Gynecol 1987; 649-676
• 3 Dornauf Ieditor , Biochemische Tests. In: Pränataldiagnostik. FertiConsult GmbH; 2002. (Online(. URL: www.gynaktuell.de/text.php3?thema=8& artikel=6&seq=23&cn=de&la=de
• 4 Snijders RJM, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre projekt on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Lancet 1998; 351: 343-346
• 5 Brambati B, Tului L, Bonacchi I, Shrimanker K, Suzuki Y, Grudzinskas JG. Serum PAPP-A and free β-hCG are first-trimester screening markers for Down syndrome. Prenat Diagn 1994; 14: 1043-1047
• 6 Wald NJ, Kenrard A, Hackshaw AK. First trimester serum screening for Down’s Syndrome. Prenat Diagn 1995; 15: 1227-1240
• 7 Brizot ML, Snijders RJM, Butler J, Bersinger NA, Nicolaides KH. Maternal serum hCG and fetalnuchal translucency thickness for the prediction of fetal trisomies in the first trimester of pregnancy. BJOG 1995; 102: 127-132
• 8 De Biasio P, Siccardi M, Volpe G, Famularo L, Santi P, Canini S. First trimester screening for Down‘s syndrome using nuchal translucency measurement with free β-hCG and PAPP-A between 10 and 13 weeks of pregnancy: the combined test. Prenat Diagn 1999; 19: 360-363
• 9 De Graaf IM, Pajkrt E, Bilardo CM, Leschot NJ, Cuckle HS, van Lith JM. Early pregnancy screening for fetal aneuploidy with serum markers and nuchal translucency. Prenat Diagn 1999; 19: 458-462
• 10 Bindra R, Heath V, Liao A, Spencer K, Nicolaides KH. One-stop clinic for assessment of risk for trisomy 21 at 11 – 14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol 2002; Sep 20 (03) 219-25
• 11 von Kaisenberg CS, Gasiorek-Wiens A, Bielicki M, Bahlmann F, Meyberg H, Kossakiewicz A, Pruggmayer M, Kamin G, Fritzer E, Harris C, Arnold N. Screening for trisomy 21 by maternal age, fetal nuchal transluecency and maternal serum biochemistry at 11–14 weeks: a German multicenter study. J Matern Fetal Neonatal Med 2002; Aug 12 (02) 89-94
• 12 Zoppi MA, Ibba RM, Floris M, Monni G.. Fetal nuchal translucency screening in 12 495 pregnancies in SardiniaUltrasound. Obstet Gynecol 2001; Dec 18 (06) 649-51
• 13 Gasiorek-Wiens A, Tercanli S, Kozlowski P, Kossakiewicz A, Minderer S, Meyberg H, Kamin G, Germer U, Bielicki M, Hackeloer BJ, Sarlay D, Kuhn P, Klapp J, Bahlmann F, Pruggmayer M, Schneider KT, Seefried W, Fritzer E, von Kaisenberg CS. Screening for trisomy 21 by fetal nuchal transluecency and maternal age: a multicenter project in Germany, Austria and SwitzerlandUltrasound . Obstet Gynecol 2001; Dec 18 (06) 645-8
• 14 Nicolaides KH, Sebire NJ, Snijders RJM. The 11–14-week scan - The diagnosis of fetal abnormalities. New York: The Parthenon Publishing Group Inc; 1999
• 15 Palomaki G, Haddow JE. Maternal serum a fetoprotein, age and Down syndrome risk. Am J Obstet Gynecol 1987; 156: 460-463
• 16 Spencer K, Spencer CE, Power M, Moakes A, Nicolaides KH. 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. BJOG 2000; 107: 1271-1275
• 17 Wald NJ, Cuckle HS. Recent advances in screening for neural tube defects and Down’s syndrome. Ballière’s Clin Obstet Gynecol 1987; 649-676
• 18 Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Downs syndrome. Prenat Diagn 1997; 17: 821-829
• 19 Zentrum für Qualitätsmanagement im Gesundheitswesen, eine Einrichtung der Ärztekammer Niedersachsen. Qualitätssicherung Geburtshilfe, Jahresauswertung 2001, Niedersachsen, Vergleichsstatistik Frauenklinik MHH Hannover 2002
• 20 Cuckle HS, Wald NJ, Densem P, Knight GJ, Haddow JE, Palomaki GE, Canick JA. The effect of smoking in pregnancy on maternal serum alphafetoprotein, unconjugated oestriol, human chorionic gonadotrophin, progesterone and dehydroepiandrosterone sulphate levels. BJOG 1990; 97: 272-276
• 21 Spencer K, Ong CY, Liao AW, Papademetriou D, Nicolaides KH. First trimester markers of trisomy 21 and the influence of maternal cigarette smoking status. Prenat Diagn 2000; 20 (10) 852-853
• 22 Crossley JA, Aitken DA, Waugh SM, Kelly T, Connor JM. Maternal smoking: age distribution, levels of alpha-fetoprotein and human chorionic gonadotrophin and effect on detection of Down syndrome pregnancies in second-trimester screening. Prenat Diagn 2002; 22 (03) 247-255
• 23 Lagerström M, Bremme K, Eneroth P. Maternal serum levels of estriol, prolactin, human placental lactogen and chorionic gonadotrophin related to fetal sex in normal and abnormal pregnancies. Gynecol Obstet Invest 1990; 30: 198-203
• 24 Spencer K, Aitken DA, Crossley JA, McGraw G, Berry E, Anderson R, Connor JM, Macri JN. First trimester biochemical screening for trisomy 21: the role of free beta hCG, alpha fetoprotein an pregnancy associated plasma protein A. Ann Clin Biochem 1994; 31: 447-454
• 25 Krantz D, Larsen J, Buchanon D, Macri J. First-trimester Down syndrome screening: free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Am J Obstet Gynecol 1996; 174: 612-616
• 26 Spencer K, Souter V, Tul N, Snijders R, Nicolaides KH. A screening program for trisomy 21 at 10–14 weeks using fetal nuchal translucency, maternal serum free beta-human chorionic gonadotropin and pregnancy associates plasma protein-A. Ultrasound Obstet Gynecol 1999; 13: 231-237
• 27 Krantz DA, Hallahan TW, Orlandi F, Buchanan P, Larsen Jr JW, Macri JN. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol 2000; 96: 207-213
• 28 Bewley S, Roberts LJ, Mackinson AM, Rodeck CH. First trimester nuchal translucency: Problems with screening the general population. 2. BJOG 1995; 102 (05) 386-388
• 29 Nicolaides KH, Brizot ML, Snijders RJM. Fetal nuchal translucency thickness: ultrasound screening for fetal trisomy in first trimester of pregnancy. BJOG 1994; 101: 782-786