Report on the 11- to 13+6-Week Ultrasound Evaluation as a Screening Test for Trisomy 21 in Singleton Pregnancies

Antoni Borrell; Julian N Robinson; Joaquin Santolaya-Forgas

doi:10.1055/s-0029-1223281

American Journal of Perinatology, Table of Contents

Am J Perinatol 2009; 26(10): 703-710
DOI: 10.1055/s-0029-1223281

Report on the 11- to 13⁺⁶-Week Ultrasound Evaluation as a Screening Test for Trisomy 21 in Singleton Pregnancies

Antoni Borrell¹ ^, ² , Julian N. Robinson² , Joaquin Santolaya-Forgas³

¹Prenatal Diagnosis Unit, Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic, Barcelona, Catalonia, Spain
²Center for Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Newton Wellesley Hospital, Newton, Massachusetts
³Center for Fetal Medicine and Prenatal Genetics, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Abstract

ABSTRACT

We sought to update the value of the 11- to 13⁺⁶-week ultrasound evaluation for prenatal screening of trisomy 21. An English literature search was conducted for pertinent original research articles, review articles, and websites related to the 11- to 13⁺⁶-week ultrasound evaluation. Reports from prenatal diagnostic units published since 1990 that included two- and three-dimensional ultrasound and Doppler hemodynamic evaluations for prenatal screening of trisomy 21 between weeks 10 and 13⁺⁶ of gestation were selected. Alternative screening methods were identified, and clinical information concerning each of them was extracted, integrated into tables, and then synthesized to provide meaningful clinical interpretations. Finally, mechanisms that could lead to improvements in the efficiency of these screening tests are discussed. Two-dimensional measurements of the fetal nuchal translucency play a key role in screening for trisomy 21. Evaluations of the nasal bone, ductus venosus, tricuspid valve function, frontomaxillary facial angle, hyperechogenic bowel, intracardiac echogenic focus, and renal pelvis fullness can become part of the 11- to 13⁺⁶-week screening test if the imaging protocols are standardized. The role of 3-D ultrasound during the 11- to 13⁺⁶-week ultrasound evaluations is under investigation.

KEYWORDS

Ultrasound - first-trimester prenatal screening - 3-D ultrasound - Doppler

Full Text

References

REFERENCES

1 Szabó J, Gellen J. Nuchal fluid accumulation in trisomy-21 detected by vaginosonography in first trimester. Lancet. 1990; 336 1133
2 Nicolaides K H, Azar G, Byrne D, Mansur C, Marks K. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ. 1992; 304 867-869
3 Pandya P P, Snijders R J, Johnson S P, De Lourdes Brizot M, Nicolaides K H. Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. Br J Obstet Gynaecol. 1995; 102 957-962
4 Snijders R J, Noble P, Sebire N, Souka A, Nicolaides K H. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet. 1998; 352 343-346
5 Wapner R, Thom E, Simpson J L First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group et al. First-trimester screening for trisomies 21 and 18. N Engl J Med. 2003; 349 1405-1413
6 Wald N J, Rodeck C, Hackshaw A K, Walters J, Chitty L, Mackinson A M. SURUSS Research Group . First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). Health Technol Assess. 2003; 7 1-77
7 Malone F D, Canick J A, Ball R H et al.. First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005; 353 2001-2011
8 Nicolaides K H. Fetal Medicine Foundation. http://www.studiolift.com/fetal/site/FMF-English.pdf Last accessed June 12, 2009
9 Abuhamad A. Technical aspects of nuchal translucency measurement. Semin Perinatol. 2005; 29 376-379
10 Nuchal Translucency Oversight Committee .Nuchal Translucency Quality Review. http://www.ntqr.org/SM/Provider/wfProviderInformation.aspx Last accessed June 12, 2009
11 Evans M I, Van Decruyes H, Nicolaides K H. Nuchal translucency measurements for first-trimester screening: the “price” of inaccuracy. Fetal Diagn Ther. 2007; 22 401-404
12 Spencer K, Bindra R, Nix A B, Heath V, Nicolaides K H. Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester?. Ultrasound Obstet Gynecol. 2003; 22 142-148
13 Gyselaers W J, Vereecken A J, Van Herck E J, Straetmans D P, Ombelet W U, Nijhuis J G. Nuchal translucency thickness measurements for fetal aneuploidy screening: Log NT-MoM or Delta-NT, performer-specific medians and ultrasound training. J Med Screen. 2006; 13 4-7
14 Wright D, Kagan K O, Molina F S, Gazzoni A, Nicolaides K H. A mixture model of nuchal translucency thickness in screening for chromosomal defects. Ultrasound Obstet Gynecol. 2008; 31 376-383
15 Palomaki G E, Neveux L M, Donnenfeld A et al.. Quality assessment of routine nuchal translucency measurements: a North American laboratory perspective. Genet Med. 2008; 10 131-138
16 Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolides K H. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet. 2001; 358 1665-1667
17 Otano L, Aiello H, Igarzábal L, Matayoshi T, Gadow E C. Association between first trimester absence of fetal nasal bone on ultrasound and Down syndrome. Prenat Diagn. 2002; 22 930-932
18 Zoppi M A, Ibba R M, Axiana C, Floris M, Manca F, Monni G. Absence of fetal nasal bone and aneuploidies at first-trimester nuchal translucency screening in unselected pregnancies. Prenat Diagn. 2003; 23 496-500
19 Orlandi F, Bilardo C M, Campogrande M et al.. Measurement of nasal bone length at 11–14 weeks of pregnancy and its potential role in Down syndrome risk assessment. Ultrasound Obstet Gynecol. 2003; 22 36-39
20 Viora E, Masturzo B, Errante G, Sciarrone A, Bastonero S, Campogrande M. Ultrasound evaluation of fetal nasal bone at 11 to 14 weeks in a consecutive series of 1906 fetuses. Prenat Diagn. 2003; 23 784-787
21 Senat M V, Bernard J P, Boulvain M, Ville Y. Intra- and interoperator variability in fetal nasal bone assessment at 11–14 weeks of gestation. Ultrasound Obstet Gynecol. 2003; 22 138-141
22 Wong S F, Ng W F, Ho L C. Histopathological findings of the nose of Down syndrome abortuses. Prenat Diagn. 2003; 23 561-563
23 Cicero S, Rembouskos G, Vandecruys H, Hogg M, Nicolaides K H. Likelihood ratio for trisomy 21 in fetuses with absent nasal bone al the 11–14-week scan. Ultrasound Obstet Gynecol. 2004; 23 218-223
24 Malone F D, Ball R H, Nyberg D A et al.. First-trimester nasal bone evaluation for aneuploidy in the general population. Obstet Gynecol. 2004; 104 1222-1228
25 Weingertner A S, Kohler M, Firtion C, Vayssière C, Favre R. Interest of foetal nasal bone measurement at first trimester trisomy 21 screening. Fetal Diagn Ther. 2006; 21 433-438
26 Kozlowski P, Knippel A J, Froehlich S, Stressig R. Additional performance of nasal bone in first trimester screening. 2006. Ultraschall Med. 2006; 27 336-339
27 Ramos-Corpas D, Santiago J C, Montoya F. Ultrasonographic evaluation of fetal nasal bone in a low-risk population at 11–13 + 6 gestational weeks. Prenat Diagn. 2006; 26 112-117
28 Prefumo F, Sairam S, Bhide A, Thilaganathan B. First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations. Am J Obstet Gynecol. 2006; 194 828-833
29 Sepulveda W, Wong A E, Dezerega V. First-trimester ultrasonographic screening for trisomy 21 using fetal nuchal translucency and nasal bone. Obstet Gynecol. 2007; 109 1040-1045
30 Moon M H, Cho J Y, Lee Y M et al.. First-trimester screening for Down syndrome; the role of nasal bone assessment in the Korean population. Prenat Diagn. 2007; 27 830-834
31 Borrell A, Borobio V, Gonce A et al.. Fetal nasal bone and ductus venosus blood flow assessed transvaginally at the 11–14 week scan—new data including unselected and high risk pregnancies. OC13. Ultrasound Obstet Gynecol. 2006; 28 362
32 Ville Y. What is the role of fetal nasal bone examination in the assessment of risk for trisomy 21 in clinical practice?. Am J Obstet Gynecol. 2006; 195 1-3
33 Peralta C FA, Falcon O, Wegrzyn P, Faro C, Nicolaides K H. Assessment of the gap between the fetal nasal bones at 11 to 13 + 6 weeks of gestation by three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2005; 25 464-467
34 Benoit B, Chaoui R. Three-dimensional ultrasound with maximal mode rendering: a novel technique for the diagnosis of bilateral or unilateral absence or hypoplasia of nasal bones in second-trimester screening for Down syndrome. Ultrasound Obstet Gynecol. 2005; 25 19-24
35 Dagklis T, Plasencia W, Maiz N, Duarte L, Nicolaides K H. Choroid plexus cyst, intracardiac echogenic focus, hyperechogenic bowel and hydronephrosis in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks. Ultrasound Obstet Gynecol. 2008; 31 132-135
36 Kiserud T, Eik-Nes S H, Blaas H G, Hellevik L R. Ultrasonographic velocimetry of the fetal ductus venosus. Lancet. 1991; 338 1412-1414
37 Borrell A, Gonce A, Martinez J M et al.. First-trimester screening for Down syndrome with ductus venosus Doppler studies in addition to nuchal translucency and serum markers. Prenat Diagn. 2005; 25 901-905
38 Matias A, Gomes C, Flack N, Montenegro N, Nicolaides K H. Screening for chromosomal abnormalities at 10–14 weeks: the role of ductus venosus blood flow. Ultrasound Obstet Gynecol. 1998; 12 380-384
39 Borrell A, Antolin E, Costa D, Farre M T, Martinez J M, Fortuny A. Abnormal ductus venosus blood flow in trisomy 21 fetuses during early pregnancy. Am J Obstet Gynecol. 1998; 179 1612-1617
40 Matias A, Huggon I, Areias J C, Montenegro N, Nicolaides K H. Cardiac defects in chromosomally normal fetuses with abnormal ductus venosus blood flow at 10–14 weeks. Ultrasound Obstet Gynecol. 1999; 14 307-310
41 Montenegro N, Matias A, Areias J C, Castedo S, Barros H. Increased fetal nuchal translucency: possible involvement of early cardiac failure. Ultrasound Obstet Gynecol. 1997; 10 265-268
42 Borrell A. The ductus venosus in early pregnancy and congenital anomalies. Prenat Diagn. 2004; 24 688-692
43 Prefumo F, Risso D, Venturini P L, De Biasio P. Reference values for ductus venosus Doppler flow measurements at 10–14 weeks of gestation. Ultrasound Obstet Gynecol. 2002; 20 42-46
44 Bilardo C M, Muller M A, Zikulnig L, Schipper M, Hecher K. Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome. Ultrasound Obstet Gynecol. 2001; 17 288-294
45 Antolin E, Comas C, Torrents M et al.. The role of ductus venosus blood flow assessment in screening for chromosomal abnormalities at 10–16 weeks of gestation. Ultrasound Obstet Gynecol. 2001; 17 295-300
46 Zoppi M A, Putzolu M, Ibba R M, Floris M, Monni G. First-trimester ductus venosus velocimetry in relation to nuchal translucency thickness and fetal karyotype. Fetal Diagn Ther. 2002; 17 52-57
47 Mavrides E, Sairam S, Hollis B, Thilaganathan B. Screening for aneuploidy in the first trimester by assessment of blood flow in the ductus venosus. BJOG. 2002; 109 1015-1019
48 Murta C GV, Moron A F, Avila M AP, Weiner C P. Application of ductus venosus Doppler velocimetry for the detection of fetal aneuploidy in the first trimester of pregnancy. Fetal Diagn Ther. 2002; 17 308-314
49 Toyama J M, Brizot M L, Liao A W et al.. Ductus venosus blood flow assessment at 11 to 14 weeks of gestation and fetal outcome. Ultrasound Obstet Gynecol. 2004; 23 341-345
50 Borrell A, Martinez J M, Seres A, Borobio V, Cararach V, Fortuny A. Ductus venosus assessment at the time of nuchal translucency measurement in the detection of fetal aneuploidy. Prenat Diagn. 2003; 23 921-926
51 Prefumo F, De Biasio P, Venturini P L. Reproducibility of ductus venosus Doppler flow measurements at 11–14 weeks of gestation. Ultrasound Obstet Gynecol. 2001; 17 301-305
52 Mavrides E, Holden D, Bland J M, Tekay A, Thilaganathan B. Intraobserver and interobserver variability of transabdominal Doppler velocimetry measurements of the fetal ductus venosus between 10 and 14 weeks of gestation. Ultrasound Obstet Gynecol. 2001; 17 306-310
53 Borrell A, Perez M, Figueras F, Meler E, Gonce A, Gratacos E. Reliability analysis on ductus venosus assessment at 11–14 weeks' gestation in a high-risk population. Prenat Diagn. 2007; 27 442-446
54 Huggon I C, DeFigueiredo D B, Allan L D. Tricuspid regurgitation in the diagnosis of chromosomal anomalies in the fetus at 11–14 weeks of gestation. Heart. 2003; 89 1071-1073
55 Faiola S, Tsoi E, Huggon I C, Allan L D, Nicolaides K H. Likelihood ratio for trisomy 21 in fetuses with tricuspid regurgitation at the 11 to 13 + 6-week scan. Ultrasound Obstet Gynecol. 2005; 26 22-27
56 Falcon O, Faiola S, Huggon I, Allan L, Nicolaides K H. Fetal tricuspid regurgitation at the 11 + 0 to 13 + 6-week scan: association with chromosomal defects and reproducibility of the method. Ultrasound Obstet Gynecol. 2006; 27 609-612
57 Falcon O, Auer M, Gerovassili A, Spencer K, Nicolaides K H. Screening for trisomy 21 by fetal tricuspid regurgitation, nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks. Ultrasound Obstet Gynecol. 2006; 27 151-155
58 McAuliffe F M, Trines J, Nield L E, Chitayat D, Jaeggi E, Hornberger L K. Early fetal echocardiography—a reliable prenatal diagnosis tool. Am J Obstet Gynecol. 2005; 193(3 Pt 2) 1253-1259
59 Smrcek J M, Krapp M, Axt-Fliedner R et al.. Atypical ductus venosus blood flow pattern in fetuses with severe tricuspid valve regurgitation. Ultrasound Obstet Gynecol. 2005; 26 180-182
60 Messing B, Porat S, Imbar T, Valsky D V, Anteby E Y, Yagel S. Mild tricuspid regurgitation: a benign fetal finding at various stages of pregnancy. Ultrasound Obstet Gynecol. 2005; 26 606-609 discussion 610
61 Falcon O, Wegrzyn P, Faro C, Peralta C F, Nicolaides K H. Gestational sac volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects. Ultrasound Obstet Gynecol. 2005; 25 546-550
62 Wegrzyn P, Faro C, Falcon O, Peralta C F, Nicolaides K H. Placental volume measured by three-dimensional ultrasound at 11 to 13 + 6 weeks of gestation: relation to chromosomal defects. Ultrasound Obstet Gynecol. 2005; 26 28-32
63 Falcon O, Cavoretto P, Peralta C F, Csapo B, Nicolaides K H. Fetal head-to-trunk volume ratio in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol. 2005; 26 755-760
64 Falcon O, Peralta C F, Cavoretto P, Auer M, Nicolaides K H. Fetal trunk and head volume in chromosomally abnormal fetuses at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol. 2005; 26 517-520
65 Falcon O, Peralta C F, Cavoretto P, Faiola S, Nicolaides K H. Fetal trunk and head volume measured by three-dimensional ultrasound at 11 + 0 to 13 + 6 weeks of gestation in chromosomally normal pregnancies. Ultrasound Obstet Gynecol. 2005; 26 263-266
66 Cicero S, Curcio P, Rembouskos G, Sonek J, Nicolaides K H. Maxillary length at 11–14 weeks of gestation in fetuses with trisomy 21. Ultrasound Obstet Gynecol. 2004; 24 19-22
67 Borenstein M, Persico N, Kaihura C, Sonek J, Nicolaides K H. Frontomaxillary facial angle in chromosomally normal fetuses at 11 + 0 to 13 + 6 weeks. Ultrasound Obstet Gynecol. 2007; 30 737-741
68 Sonek J, Borenstein M, Dagklis T, Persico N, Nicolaides K H. Frontomaxillary facial angle in fetuses with trisomy 21 at 11–13(6) weeks. Am J Obstet Gynecol. 2007; 196 e1-e4
69 Borenstein M, Persico N, Strobl I, Sonek J, Nicolaides K H. Frontomaxillary and mandibulomaxillary facial angles at 11 + 0 to 13 + 6 weeks in fetuses with trisomy 18. Ultrasound Obstet Gynecol. 2007; 30 928-933
70 Borenstein M, Persico N, Dagklis T, Faros E, Nicolaides K H. Frontomaxillary facial angle in fetuses with trisomy 13 at 11 + 0 to 13 + 6 weeks. Ultrasound Obstet Gynecol. 2007; 30 819-823
71 Faro C, Wegrzyn P, Benoit B, Chaoui R, Nicolaides K H. Metopic suture in fetuses with trisomy 21 at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol. 2006; 27 286-289
72 Faro C, Wegrzyn P, Benoit B, Chaoui R, Nicolaides K H. Metopic suture in fetuses with holoprosencephaly at 11 + 0 to 13 + 6 weeks of gestation. Ultrasound Obstet Gynecol. 2006; 27 162-166
73 Rembouskos G, Cicero S, Longo D, Vandecruys H, Nicolaides K H. Assessment of the fetal nasal bone at 11–14 weeks of gestation by three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2004; 23 232-236
74 Krantz D A, Hallahan T W, Orlandi F, Buchanan P, Larsen J W, Macri J N. First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Obstet Gynecol. 2000; 96 207-213
75 Niemimaa M, Suonpaa M, Perheentupa A et al.. Evaluation of first trimester maternal serum and ultrasound screening for Down's syndrome in Eastern and Northern Finland. Eur J Hum Genet. 2001; 9 404-408
76 Schuchter K, Hafner E, Stangi G, Metzenbauer M, Hofinger D, Philipp K. The first trimester “combined test” for the detection of Down syndrome pregnancies in 4939 unselected pregnancies. Prenat Diagn. 2002; 22 211-215
77 von Kaisenberg C S, Gasiorek-Wiens A, Bielicki M et al.. Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11–14 weeks: a German multicenter study. J Matern Fetal Neonatal Med. 2002; 12 89-94
78 Stenhouse E J, Crossley J A, Aitken D A, Brogan K, Cameron A D, Connor J M. First-trimester combined ultrasound screening for Down syndrome in routine clinical practice. Prenat Diagn. 2004; 24 774-780
79 Bach C, Torrent S, Cabrero D, Sabrià J. Cribado bioquímico-ecográfico de las aneuploidías en el primer trimestre. Metodología y resultados. Prog Obstet Ginecol. 2004; 47 5-19
80 Wøjdemann K R, Shalmi A C, Christiansen M et al.. Improved first-trimester Down syndrome screening performance by lowering the false-positive rate: a prospective study of 9941 low-risk women. Ultrasound Obstet Gynecol. 2005; 25 227-233
81 Hadlow N C, Hewitt B G, Dickinson J E, Jacoby P, Bower C. Community-based screening for Down's syndrome in the first trimester using ultrasound and maternal serum biochemistry. BJOG. 2005; 112 1561-1564
82 Nicolaides K H, Spencer K, Avgidou K, Faiola S, Falcon O. 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
83 Borrell A, Casals E, Fortuny A et al.. First-trimester screening for trisomy 21 combining biochemistry and ultrasound at individually optimal gestational ages. An interventional study. Prenat Diagn. 2004; 24 541-545
84 Cicero S, Avgidou K, Rembouskos G, Kagan K O, Nicolaides K H. Nasal bone in first-trimester screening for trisomy 21. Am J Obstet Gynecol. 2006; 195 109-114
85 Weisz B, Pandya P, Chitty L, Jones P, Huttly W, Rodeck C. Practical issues drawn from the implementation of the integrated test for Down syndrome screening into routine clinical practice. BJOG. 2007; 114 493-497
86 Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A. Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol. 2006; 6 31

Antoni BorrellM.D. Ph.D.

Prenatal Diagnosis Unit, Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic

Maternitat Campus, Sabino Arana 1. 08028 Barcelona Catalonia, Spain

Email: aborrell@clinic.ub.es