The Value of Detailed First-Trimester Ultrasound Anomaly Scan for the Detection of Chromosomal Abnormalities

Abstract

Purpose To evaluate the performance of first-trimester ultrasound screening involving a detailed anomaly scan for the detection of trisomy 18, trisomy 13, triploidy, Turner syndrome and trisomy 21.

Methods Data of pregnant women who underwent aneuploidy screening at 11–13 weeks of gestation was retrospectively analyzed. Crown-rump length (CRL), fetal nuchal translucency thickness (NT) and nasal bone (NB) anatomy, blood flow across the tricuspid valve (TV) and through the ductus venosus (DV) were assessed. Furthermore, a detailed scan for fetal anatomical anomalies (FA) was carried out. Performance of these markers was assessed by logistic regression and ROC analyses for different screening models.

Results 4005 fetuses were analyzed. 3856 were euploid, 149 aneuploid (trisomy 18: 40; trisomy 13: 14; triploidy: 3; Turner syndrome: 17; trisomy 21: 75 cases). 70–100 % of the fetuses with trisomy 18 and 13, triploidy and Turner syndrome but only 34.7 % with trisomy 21 had at least one fetal defect. Considering all aneuploidies, the detection rate (DR) for screening based on MA+NT+NB+TV+DV was 90.6 % and improved to 96.0 % if an FA was added (fixed false-positive rate: 3 %). If screening was based on MA+NT+FA, the detection rate for all aneuploidies was 85.2 %. However, the DR for trisomy 18, trisomy 13, triploidy and Turner syndrome (excluding trisomy 21) was 94.6 %, indicating the high diagnostic value of an anomaly scan for these aneuploidies.

Conclusion Incorporation of a detailed fetal anomaly scan (FA) into first-trimester screening algorithms can improve the detection rates for trisomy 18 and 13, triploidy and Turner syndrome.

Zusammenfassung

Ziel Ziel der Studie war es, die diagnostische Güte einer detaillierten Organdiagnostik im Rahmen eines Ersttrimester-Ultraschallscreenings für Trisomie 18, Trisomie 13, Triploidie, Turner Syndrom und Trisomie 21 zu ermitteln.

Methode Daten schwangerer Frauen, bei denen ein Ultraschallscreening zur Detektion von Aneuploidien zwischen 11 und 13 Schwangerschaftswochen durchgeführt worden war, wurden retrospektiv analysiert. Berücksichtigt wurden Scheitel-Steiß-Länge (CRL), Nackentransparenz (NT), Anatomie des Nasenbeins (NB), Blutfluss über die Trikuspidalklappe (TV) und durch den Ductus venosus (DV). Außerdem wurde eine detaillierte Ultraschalluntersuchung auf anatomische Fehlbildungen (FA) durchgeführt. Die Detektionsleistung dieser Marker wurde durch logistische Regression und ROC-Analyse für verschiedene Screening-Modelle ermittelt.

Ergebnisse 4005 Feten wurden analysiert. 3856 waren euploid, 149 aneuploid (Trisomie 18: 40; Trisomie 13: 14; Triploidy: 3; Turner Syndrome: 17; Trisomy 21: 75 Fälle). 70–100 % der Feten mit Trisomie 18 und 13, Triploidie und Turner Syndrome aber nur 34,7 % mit Trisomy 21 wiesen mindestens einen fetalen Defekt auf. Die Detektionsrate (DR) für diese Aneuploidien mit einem Screening-Modell basierend auf MA+NT+NB+TV+DV betrug 90,6 %. Durch Hinzunahme eines FA konnte sie auf 96 % gesteigert werden (Falsch-positiv-Rate: 3 %). Für ein Screening basierend auf MA+NT+FA betrug die DR 85,2 %. Wurden jedoch lediglich Trisomie 18 und 13, Triploidie und Turner Syndrom betrachtet (ohne Trisomie 21), betrug die DR 94,6 %. Die diagnostische Güte einer detaillierten Organdiagnostik ist also für diese Aneuploidien besonders hoch.

Schlussfolgerung Die Hinzunahme einer detaillierten Organdiagnostik zum Screening-Algorithmus im ersten Trimester kann die Entdeckungsraten für Trisomie 18, Trisomie 13, Triploidie und Turner Syndrom verbessern.

Key words

first trimester - aneuploidy - ultrasound screening - fetal defects - obstetrics

• References

• 1 Loane M, Morris JK, Addor MC. et al. Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening. Eur J Hum Genet 2013; 21: 27-33
• 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 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
• 4 Engelbrechtsen L, Brondum-Nielsen K, Ekelund C. et al. Detection of triploidy at 11–14 weeks’ gestation: a cohort study of 198 000 pregnant women. Ultrasound Obstet Gynecol 2013; 42: 530-535
• 5 Kagan KO, Anderson JM, Anwandter G. et al. Screening for triploidy by the risk algorithms for trisomies 21, 18 and 13 at 11 weeks to 13 weeks and 6 days of gestation. Prenat Diagn 2008; 28: 1209-1213
• 6 Kagan KO, Cicero S, Staboulidou I. et al. Fetal nasal bone in screening for trisomies 21, 18 and 13 and Turner syndrome at 11–13 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 259-264
• 7 Kagan KO, Valencia C, Livanos P. et al. Tricuspid regurgitation in screening for trisomies 21, 18 and 13 and Turner syndrome at 11+0 to 13+6 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 18-22
• 8 Maiz N, Valencia C, Kagan KO. et al. Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11–13 weeks of gestation. Ultrasound Obstet Gynecol 2009; 33: 512-517
• 9 Maiz N, Wright D, Ferreira AF. et al. A mixture model of ductus venosus pulsatility index in screening for aneuploidies at 11–13 weeks’ gestation. Fetal Diagn Ther 2012; 31: 221-229
• 10 Wagner P, Sonek J, Hoopmann M. et al. First-trimester screening for trisomies 18 and 13, triploidy and Turner syndrome by detailed early anomaly scan. Ultrasound Obstet Gynecol 2016; 48: 446-451
• 11 Gil MM, Quezada MS, Revello R. et al. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 2015; 45: 249-266
• 12 Taylor-Phillips S, Freeman K, Geppert J. et al. Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis. BMJ Open 2016; 6: e010002
• 13 Salomon LJ, Alfirevic Z, Audibert F. et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol 2014; 44: 122-123
• 14 Von Kaisenberg CS, Chaoui R, Häusler M. et al. Quality Requirements for the early Fetal Ultrasound Assessment at 11–13+6 Weeks of Gestation (DEGUM Levels II and III). Ultraschall in Med 2016; 37: 297-302
• 15 Schmid M, Klaritsch P, Arzt W. et al. Cell-Free DNA Testing for Fetal Chromosomal Anomalies in clinical practice: Austrian-German-Swiss Recommendations for non-invasive prenatal tests (NIPT). Ultraschall in Med 2015; 36: 507-510
• 16 Robinson HP, Fleming JE. A critical evaluation of sonar “crown-rump length” measurements. Br J Obstet Gynaecol 1975; 82: 702-710
• 17 Hyett JA, Moscoso G, Nicolaides KH. First-trimester nuchal translucency and cardiac septal defects in fetuses with trisomy 21. Am J Obstet Gynecol 1995; 172: 1411-1413
• 18 Paladini D, Tartaglione A, Agangi A. et al. The association between congenital heart disease and Down syndrome in prenatal life. Ultrasound Obstet Gynecol 2000; 15: 104-108
• 19 Wiechec M, Knafel A, Nocun A. et al. How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound Only?. Fetal Diagn Ther 2016; 39: 105-112
• 20 Kagan KO, Hoopmann M, Hammer R. et al. Screening for chromosomal abnormalities by first trimester combined screening and noninvasive prenatal testing. Ultraschall in Med 2015; 36: 40-46