Screening auf Trisomie 18 und Trisomie 13 durch das kombinierte Anwenden der Risiko-Algorithmen für Trisomie 21, 18 und 13

Zusammenfassung

Ziel: Beurteilung der Testgüte des kombinierten Ersttrimester-Screenings auf Trisomien 18 und 13 bei gemeinsamer Verwendung der Risikoalgorithmen für Trisomie 21, 18 und 13 in einem deutschen Patientenkollektiv.

Material und Methoden: Bei 39 004 Schwangerschaften wurde zwischen 2002 und 2007 im Rahmen des Ersttrimester-Screenings die fetale NT, PAPP-A und freies β-hCG gemessen. Im Rahmen dieser Studie erfolgte die erneute Auswertung der Trisomie-21-, -18- und -13-Risiken mit dem aktuellen Algorithmus der FMF London.

Ergebnisse: 38 751 Einlingsschwangerschaften, darunter 39 Fälle einer Trisomie 18 oder Trisomie 13, konnten in die Auswertung einbezogen werden. In diesen Fällen lag die mediane delta NT bei 0,72 mm, PAPP-A bei 0,21 MoM und das freie β-hCG bei 0,33 MoM. Die NT lag nur bei 41 % der Trisomie-18/13-Fälle oberhalb der 95. Perzentile. Die alleinige Anwendung des Trisomie-18/13-Algorithmus führte bei einem Cut-off von 1:100 zu einer Detektionsrate für die Trisomien 18/13 von 82 % bei einer Falsch-Positivrate von 0,7 %. Bei alleiniger Verwendung des Trisomie-21-Algorithmus mit einem Cut-off 1:200 wurden bei einer Falsch-Positivrate von 4,7 % 56,4 % der Trisomie-18/13-Fälle erkannt. Bei kombinierter Anwendung beider Algorithmen mit gleichen Cut-off-Werten stieg die Trisomie-18/13-Detektionsrate auf etwa 94,9 %. Die Falsch-Positivrate stieg dabei aber nur um 0,3 auf 5,0 %.

Schlussfolgerung: Die gemeinsame Anwendung des Trisomie-21-, -18- und -13-Algorithmus der FMF London führt unter Routinebedingungen trotz der Unterschätzung der NT zu einer 95 %-Detektionsrate für die Trisomien 18 und 13.

Abstract

Purpose: Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13.

Materials and Methods: First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free β-hCG was assessed in 39 004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm.

Results: The study population consisted of 38 751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free β-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95^th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %.

Conclusion: Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.

Key words

nuchal translucency - screening - serum biochemistry - first trimester

• Literatur

• 1 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
• 2 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
• 3 Nicolaides KH, Spencer K, Avgidou K et al. Multicenter study of first-trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk-orientated two-stage first-trimester screening. Ultrasound Obstet Gynecol 2005; 25: 221-226
• 4 Lüthgens K. Comparison of the new PRC software with the established algorithm of the FMF UK for the detection of trisomy 21 and 18/13. Fetal Diagn Ther 2008; 24: 376-384
• 5 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 beta-hCG and pregnancy-associated plasma protein-A. Hum Reprod 2008; 23: 1968-1975
• 6 Kagan KO, Wright D, Maiz N et al. Screening for trisomy 18 by maternal age, fetal nuchal translucency, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008; 32: 488-492
• 7 Spencer K, Ong C, Skentou H et al. Screening for trisomy 13 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10–14 weeks of gestation. Prenat Diagn 2000; 20: 411-416
• 8 Spencer K, Nicolaides KH. A first trimester trisomy 13/ trisomy 18 risk algorithm combining fetal nuchal translucency thickness, maternal serum free beta-hCG and PAPP-A. Prenat Diagn 2002; 22: 877-879
• 9 Snijders RJ, Noble P, Sebire N et al. UK multicentre project 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
• 10 Snijders RJM, Sundberg K, Holzgreve W et al. Maternal age and gestation – specific risk for trisomy 21. Ultrasound Obstet Gynecol 1999; 13: 167-170
• 11 Snijders RJM, Sebire NJ, Cuckle H et al. Maternal age and gestational age-specific risks for chromosomal defects. Fetal Diagn Ther 1995; 10: 356-367
• 12 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
• 13 Kagan KO, Wright D, Spencer K et al. First-trimester screening for trisomy 21 by free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A: impact of maternal and pregnancy characteristics. Ultrasound Obstet Gynecol 2008; 31: 493-502
• 14 McKay HT. Elective Termination of Pregnancy. In: Leppert PC, Peipert JF. Primary Care for Women. 2nd Edition. Lippincott Williams & Wilkins; 2004
• 15 Bartlett LA, Berg CJ, Shulman HB et al. Risk factors for legal induced abortion related mortality in the United States. Obstet Gynecol 2004; 103: 729-737
• 16 Lüthgens K, Abele H, Alkier R et al. Cross-Validierung des Screening-Algorithmus der FMF London an 39000 Ersttrimester-Untersuchungen in Deutschland. Ultraschall in Med . In press.
• 17 Merz E, Thode C, Eiben B et al. Individualized Correction for Maternal Weight in Calculating the Risk of Chromosomal Abnormalities with First-Trimester Screening Data. Ultraschall in Med 2011; 32: 33-39
• 18 Breathnach FM, Malone FD, Lambert-Messerlian G et al. First- and second-trimester screening: detection of aneuploidies other than Down syndrome. Obstet Gynecol 2007; 110: 651-657