Suspicious Prenasal Skin Thickness-to-Nasal Bone Length Ratio: Prevalence and Correlation with Other Markers in Second and Third Trimester Fetuses with Down Syndrome

Abstract

Purpose: To assess the prevalence and value of a suspicious prenasal skin thickness-to-nasal bone length ratio (PT/NB ratio) in comparison to other established markers in a large population of Down syndrome (DS) fetuses.

Materials and Methods: This was a retrospective study of 139 DS fetuses and 530 normal fetuses scanned after 14 + 0 weeks of gestation. To characterize diagnostic performance, we used the ROC curve approach. The presence or absence of a PT/NB ratio > 0.8 and 11 other markers were assessed in the group of DS fetuses. A correlation analysis was performed in order to investigate associations between PT/NB ratio and other markers.

Results: Among DS fetuses the median PT/NB ratio was 1.06 (IQR 0.729) and was significantly higher compared to normal fetuses with 0.62 (IQR 0.148), (p < 0.001). Gestational age had no influence on the PT/NB ratio. A PT/NB ratio > 0.8 had the highest prevalence of all markers with 89.2 % in the group of DS fetuses, 3 cases were negative for all markers and 3 cases were positive only for PT/NB ratio > 0.8. Marker-specific comparison between prevalences of a suspicious PT/NB ratio with respect to the presence or absence of other markers was statistically significant for hypoplastic NB and major anomalies (p < 0.05). Utilization of at least one of the following five markers was sufficient for detecting 136 out of 139 fetuses with trisomy 21: suspicious PT/NB ratio, hypoplastic NB, nuchal fold thickness, white spot, shortened femur.

Conclusion: The PT/NB ratio is one of the most powerful indicators of DS in the second trimester. It is objective to interpret, easy to measure, and is reproducible.

Zusammenfassung

Ziel: Untersuchung der Prävalenz einer auffälligen Ratio von präfrontaler Hautdicke und Nasenbeinlänge (PT/NB-Ratio) in einer größeren Population von Feten mit Down-Syndrom (DS) im zweiten und dritten Trimenon sowie die Beurteilung des Stellenwerts und der Korrelation gegenüber anderen etablierten Markern.

Material und Methoden: Es handelt sich um eine retrospektive Analyse von 139 Feten mit DS und 530 gesunden Feten ab 14 + 0 Schwangerschaftswochen. Die diagnostische Güte wurde mittels ROC-Kurven charakterisiert. Des Weiteren wurde die Prävalenz einer auffälligen PT/NB-Ratio (cut off > 0,8) und 11 anderer etablierter DS Marker bestimmt. Mit einer Korrelationsanalyse wurden mögliche Zusammenhänge einer auffälligen PT/NB-Ratio mit anderen der genannten Marker untersucht.

Ergebnisse: Bei Feten mit DS lag der Median der PT/NB-Ratio bei 1,06 (IQR 0,729) und damit signifikant höher als bei gesunden Feten mit 0,62 (IQR 0.148) (p < 0,001). Das Gestationsalter hatte keinen Einfluß auf die PT/NB-Ratio. Bei den Feten mit DS hatte eine PT/NB-Ratio > 0,8 die höchste Prävalenz aller Marker mit 89,2 %. In 3 Fällen von DS waren alle Marker negative. Gleichfalls in 3 Fällen war eine auffällige PT/NB-Ratio der einzige positive Marker. Bei der Untersuchung der Korrelation mit anderen Markern ergab sich eine signifikante Zunahme der Prävalenz für Fälle mit gleichzeitig bestehenden schweren Fehlbildungen oder bei Nachweis eines hypoplastischen Nasenbeins (p < 0,05). Bei 136 von 139 Feten war immer zumindest einer der folgenden Marker nachweisbar: PT/NB-Ratio > 0,8, hypoplastisches NB, Nackenödem, white spot, verkürzter Femur.

Schlussfolgerung: Die auffällige PT/NB-Ratio ist einer der wichtigsten Marker für das DS im 2. und 3. Trimenon. Er ist einfach zu messen, leicht reproduzierbar und unterliegt keiner subjektiven Interpretation.

Key words

prenasal skin thickness - nasal bone length - trisomy 21

• References

• 1 Kagan K, Eiben B, Kozlowski P. Combined First Trimester Screening and Cell-Free Fetal DNA – “Next Generation Screening”. Ultraschall in Med 2014; 35: 229-236
• 2 Guis F, Ville Y, Vincnt Y et al. Ultrasound evaluation of the length of the fetal nasal bones throughout gestation. Ultrasound Obstet Gynecol 1995; 5: 304-307
• 3 Maymon R, Levinsohn-Tavor O, Cuckle H et al. Second trimester ultrasound prenasal thickness combined with nasal bone length: a new method of Down syndrome screening. Prenatal Diagnosis 2005; 25: 906-911
• 4 Persico N, Borenstein M, Molina F et al. Prenasal Thickness in trisomy-21 fetuses at 16–24 weeks of gestation. Ultrasound Obstet Gynecol 2008; 32: 247-261
• 5 Vos FI, de Jong-Pleij EAP, Bakker M et al. Nasal bone length, prenasal thickness, prenasal thickness to nasal bone length ratio and the prefrontal space ratio in second and third trimester Down syndrome. Ultrasound Obstet and Gynecol Online-Publikation; 2014;
• 6 Down LJ. Observations on an ethnic classification of idiots. Clinical lectures and Reports. London Hospital; 1866 3. 259-262
• 7 Sonek JD, Nicolaides KH. Prenatal ultrasonographic diagnosis of nasal bone abnormalities in three fetuses with Down syndrome. Am J Obstet Gynecol 2002; 186: 139-141
• 8 Cicero S, Sonek JD, McKenna DS et al. Nasal bone hypoplasia in trisomy 21 at 15–22 weeks’ gestation. Ultrasound Obstet Gynecol 2003; 21: 15-18
• 9 Maymon R, Moskovitch M, Levinsohn-Tavor O et al. Bedside estimation of Down syndrome risk from second-trimester ultrasound prenasal thickness. Ultrasound Obstet Gynecol 2009; 34: 629-633
• 10 Yazdi B, Sonek J, Oettling C et al. Prefrontal space ratio in second- and third-trimester screening for trisomy 21. Ultrasound Obstet Gynecol 2013; 41: 262-266
• 11 Sonek J, Molina F, Hiett AK et al. Prefrontal space ratio: comparison between trisomy 21 and euploid fetuses in the second trimester. Ultrasound Obstet Gynecol 2012; 40: 293-296
• 12 Miguelez J, Moskovitch M, Cuckle H et al. Model-Predicted Performance of Second-Trimester Down Syndrome Screening With Sonographic Prenasal Thickness. J Ultrasound Med 2010; 29: 1741-1747
• 13 De Jong-PleiJ EAP, Vos FI, Ribbert LSM et al. Prenasal thickness-to-nasal bone length: a strong and simple second- and third-trimester marker for trisomy 21. Ultrasound Obstet Gynecol 2012; 39: 185-190
• 14 Vos FI, De Jong-Pleij EAP, Ribbert LSM et al. Three-dimensional ultrasound imaging and measurement of nasal bone length, prenasal thickness and frontomaxillary facial angle in normal second- and third-trimester fetuses. Ultrasound Obstet Gynecol 2012; 39: 636-641
• 15 Gonzales R, Aedo S, Dezerega V et al. Frontonasal Fold Thickness-to-Nasal Bone Length Ratio as a Prenatal Sonographic Marker for Trisomy 21 in a Low-Risk Population. J Ultrasound Med 2013; 32: 795-800
• 16 Maymon R, Ushakov F, Waisman D et al. A model for second-trimester Down syndrome sonographic screening based on facial landmarks and digit length measurement. Ultrasound Obstet Gynecol 2006; 27: 290-295
• 17 Sonek JD, McKenna D, Webb D et al. Nasal bone length throughout gestation: normal ranges based on 3537 fetal ultrasound measurements. Ultrasound Obstet Gynecol 2003; 21: 152-155
• 18 Ulreich S, Gruslin A, Nodell CG et al. Fetal Hydrops and Ascites. In: Nyberg DA, McGahan JP, Pretorius DH, et al. (eds) Diagnostic Imaging of Fetal Anomalies. Lippincot Williams & Wilkins; 2003: 728-729
• 19 Jeanty P, Valero G, Bircher AM et al. Skeletal Dysplasias. In: Nyberg DA, McGahan JP, Pretorius DH, et al. (eds) Diagnostic Imaging of Fetal Anomalies. Lippincot Williams & Wilkins; 2003: 673-674
• 20 Nyberg DA, Souer VL, El-Bastawissi A et al. Isolated Sonographic Markers for Detection of Fetal Down Syndrome in the Second Trimester of Pregnancy. J Ultrasound Med 2001; 20: 1053-1063
• 21 Persico N, Molina F, Borenstein M et al. Nasal-bone length in euploid fetuses at 16–24 weeks’ gestation by three-dimensional ultrasound. Ultrasound Obstet Gynecol 2010; 36: 285-290
• 22 Agathokleous M, Chaveeva P, Poon LCY et al. Meta-analysis of second-trimester markers for trisomy 21. Ultrasound Obstet Gynecol 2013; 41: 247-261
• 23 Bromley B, Liebermann E, Shipp TD et al. The Genetic Sonogram. A Method of Risk Assessment for Down Syndrome in the Second Trimester. J Ultrasound Med 2002; 21: 1087-1096
• 24 Aagaard-Tillery KM, Malone FD, Nyberg DA et al. Role of Second-Trimester Genetic Sonography After Down Syndrome Screening. Obstetrics & Gynecology 2009; 114: 1189-1196
• 25 Nicolaides KH. Screening for chromosomal defects. Ultrasound Obstet Gynecol 2003; 21: 313-321
• 26 Berg C, Kaiser C, Bender F et al. Atrioventricular septal defect in the fetus: associated conditions and outcome in 246 cases. Ultraschall in Med 2009; 308: 25-32
• 27 Miguelez J, De Lourdes BM, Liao AW et al. Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies. Ultrasound Obstet Gynecol 2012; 39: 274-278
• 28 Odibo AO, Sehdev HM, Sproat L et al. Evaluating the Efficiency of Using Second-Trimester Nasal Bone Hypoplasia as a Single or a Combined Marker for Fetal Aneuploidy. J Ultrasound Med 2006; 25: 437-441
• 29 Lau TK, Evans MI. Second-trimester sonographic soft markers: what can we learn from the experience of first trimester nuchal translucency screening?. Ultrasound Obstet Gynecol 2008; 32: 121-125