Cross-Validierung des Screening-Algorithmus der FMF London an 38 700 Ersttrimester-Untersuchungen in Deutschland

Zusammenfassung

Ziel: Überprüfung der Testgüte des Algorithmus der FMF London für das Screening auf Trisomie 21 im ersten Trimester mittels Nackentransparenz (NT), PAPP-A und freiem β-hCG in einem deutschen Patientenkollektiv. Material und Methoden: In 39 004 Schwangerschaften wurde zwischen 2002 und 2007 im Rahmen des Ersttrimester-Screenings die NT, PAPP-A und freies β-hCG gemessen und die Trisomie-21-Risiken mit dem jeweils gültigen Algorithmus der FMF London berechnet. Im Rahmen dieser Studie erfolgte die erneute Auswertung der Trisomie-21-Risiken mit dem neuen Algorithmus der FMF London, der für die NT das Mixture Model verwendet. Ergebnisse: 38 751 Fälle mit Einlingsschwangerschaften konnten in die Auswertung einbezogen werden. Bei 109 Fällen wurde eine Trisomie 21 nachgewiesen. Nur 35 % der NT-Messwerte euploider Feten lagen oberhalb des Medianwerts der FMF London und in 25 % der Fälle wurde ein NT-Wert unterhalb der 5. Perzentilenkurve der FMF London gemessen. Die mediane NT von Feten mit Trisomie 21 lag bei Auswertung durch DEGUM-II/III-qualifizierte Frauenärzte 0,9 mm oberhalb des Medians, bei Auswertung durch nicht entsprechend qualifizierte Frauenärzte nur 0,5 mm oberhalb des Medians der FMF London. Trotz der eingeschränkten Performance der NT-Messung betrug die Erkennungsrate, jeweils unter Berücksichtigung des mütterlichen Alters, bei einer 5 %igen Falsch-Positivrate 90,8 % für die Kombination aus NT + Biochemie. Die Falsch-Positivrate betrug bei einem Cut-off von 1:300 zum Zeitpunkt der Untersuchung 6,5 %. Schlussfolgerung: Diese Studie konnte zeigen, dass trotz in Deutschland überwiegend zu klein gemessener NT durch Anwendung des neuen Algorithmus der FMF London in Kombination mit der Serum-Biochemie eine Detektionsrate der Trisomie 21 von ca. 90 % bei 5 % Falsch-Positivrate erreicht wird.

Abstract

Purpose: Validation of the performance of the new algorithm of the FMF London for screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free β-hCG and PAPP-A. Materials and Methods: Between 2002 and 2007, NT was measured prospectively in 39 004 pregnancies in the context of routinely performed first trimester screening in Germany. Individual trisomy 21 risks were calculated by a combination of NT, maternal age, free β-hCG, and PAPP-A using the FMF algorithm in force at the time of investigation. In this study we recalculated the trisomy 21 risks applying the new algorithm of the FMF UK that includes the new mixture model for the NT measurement. Results: 38 751 singleton pregnancies could be included in the study of which 109 (0.3 %) had a trisomy 21. Only 35 % of the NT measurements of euploids were above the median and 25 % of the NT measurements were below the 5th percentile of the FMF UK. For sonographers that were qualified according to level II or III of the German DEGUM system, the median NT of fetuses with trisomy 21 was 0.9 mm above the median of the FMF UK and only 0.5 mm above the median for all other sonographers. Despite the limited performance of the NT measurement, the overall detection rate for a trisomy 21 was 90.8 % when combining the NT with maternal age, PAPP-A and free β-hCG. The overall false-positive rate for a trisomy 21 was 6.5 % at a cut-off value of 1:300. Conclusion: In this study we were able to show that the use of the new risk algorithm of the FMF UK leads to a trisomy 21 detection rate of about 90 % at a 5 % false-positive rate in a German collective despite a significant underestimation of the NT.

Key words

nuchal translucency - first trimester - screening - serum biochemistry

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