Archives of Gynecology and Obstetrics

, Volume 299, Issue 4, pp 939–945 | Cite as

Down’s syndrome screening at 11–14 weeks' gestation using prenasal thickness and nasal bone length

  • Gwendolin Manegold-BrauerEmail author
  • Ron Maymon
  • Shimrit Shor
  • Howard Cuckle
  • Ulrich Gembruch
  • Annegret Geipel
Maternal-Fetal Medicine



To perform a multicenter prospective study of ultrasound prenasal thickness (PT), and nasal bone length (NBL) measurement at 11–14 weeks’ gestation.


Ultrasound PT and NBL determination was performed in 504 normal fetuses and 17 fetuses with Down's syndrome (DS). Measurements were made from mid-sagittal 2D images acquired using a standardized technique during nuchal translucency (NT) examination. PT and NBL values were expressed in multiples of the gestation-specific normal median (MoM) and as the PT/NBL ratio. Information on PT and NBL MoMs was also combined using logistic regression. Results were classified as positive according to whether they were greater than the normal 95th centile for PT, PT/NBL and the DS risk from logistic regression equation or below the 5th centile for NBL.


The median value in DS cases and unaffected controls were: PT 1.26 and 0.996 MoM; and NBL 0.596 and 0.993 MoM. The proportion of DS fetuses with positive results was 41% for PT, 65% for NBL, and 82% for both the PT/NBL ratio and DS risk from the logistic regression equation. PT/NBL levels did not vary according to gestational age.


The PT/NBL ratio is a valuable first trimester DS screening marker that can be easily determined concomitant with the NT measurement.


First trimester Prenasal thickness Nasal bone length Down's syndrome Screening 


Author contributions

GMB: project development, data collection, data analysis, and manuscript writing. RM: data collection and manuscript writing/editing. SS: data collection. HC: data analysis and manuscript writing/editing. UG: project development and manuscript editing. AG: project development, data collection, data analysis and manuscript writing/editing.


There was no funding for this study.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest. The authors state that they had full control of all primary data and that they agree to allow the Journal to review their data if requested.

Ethical standards

Ethical approval for the study was granted by the Ethics Committee of Central- and Northwest-Switzerland (EKNZ, Basel, Switzerland), No. 2016-01414. Approval was additionally obtained the two other participating centers (center 1: No. 053/17, center 2: No. 136/16). According to local regulations, informed consent was not obtained and not required for this anonymized data analysis. Patients were not included if they explicitly refused further use of their anonymized data.


  1. 1.
    Sonek J, Borenstein M, Dagklis T, Persico N, Nicolaides KH (2007) Frontomaxillary facial angle in fetuses with trisomy 21 at 11–136 weeks. Am J Obstet Gynecol 196:271.e1–271.e4CrossRefGoogle Scholar
  2. 2.
    Sonek JD, Cicero S, Neiger R, Nicolaides KH (2006) Nasal bone assessment in prenatal screening for trisomy 21. Am J Obstet Gynecol 195:1219–1230CrossRefGoogle Scholar
  3. 3.
    Cicero S, Longo D, Rembouskos G, Sacchini C, Nicolaides KH (2003) Absent nasal bone at 11–14 weeks of gestation and chromosomal defects. Ultrasound Obstet Gynecol 22:31–35CrossRefGoogle Scholar
  4. 4.
    Maymon R, Mendlovic S, Melcer Y, Sarig-Meth T, Habler L, Cuckle H, Vaknin Z (2017) Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: sonographic and immunohistological findings. J Perinat Med 45:213–218CrossRefGoogle Scholar
  5. 5.
    Maymon R, Levinsohn-Tavor O, Cuckle H, Tovbin Y, Dreazen E, Wiener Y, Herman A (2005) Second trimester ultrasound prenasal thickness combined with nasal bone length: a new method of Down syndrome screening. Prenat Diagn 25:906–911CrossRefGoogle Scholar
  6. 6.
    Persico N, Borenstein M, Molina F, Azumendi G, Nicolaides KH (2008) Prenasal thickness in trisomy-21 fetuses at 16–24 weeks of gestation. Ultrasound Obstet Gynecol 32:751–754CrossRefGoogle Scholar
  7. 7.
    Vos FI, De Jong-Pleij EAP, Ribbert LSM, Tromp E, Bilardo CM (2012) 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 39:636–641CrossRefGoogle Scholar
  8. 8.
    De Jong-Pleij EAP, Vos FI, Ribbert LSM, Pistorius LR, Tromp E, Bilardo CM (2012) Prenasal thickness-to-nasal bone length ratio: a strong and simple second- and third-trimester marker for trisomy 21. Ultrasound Obstet Gynecol 39:185–190CrossRefGoogle Scholar
  9. 9.
    Szabó A, Szili K, Szabó JT, Sikovanyecz J, Isaszegi D, Horváth E, Szabó J (2014) Nasal bone length: prenasal thickness ratio: a strong 2D ultrasound marker for Down syndrome. Prenat Diagn 34:1139–1145CrossRefGoogle Scholar
  10. 10.
    Ozcan T, Özlü T, Allen J, Peterson J, Pressman EK (2013) Predictive role of prenasal thickness and nasal bone for Down syndrome in the second trimester. Eur J Obstet Gynecol Reprod Biol 171:220–224CrossRefGoogle Scholar
  11. 11.
    Vos FI, De Jong-Pleij EAP, Bakker M, Tromp E, Pajkrt E, Kagan KO, Bilardo CM (2015) Nasal bone length, prenasal thickness, prenasal thickness-to-nasal bone length ratio and prefrontal space ratio in second- and third-trimester fetuses with Down syndrome. Ultrasound Obstet Gynecol 45:211–216CrossRefGoogle Scholar
  12. 12.
    Miguelez J, Maymon R, Cuckle H, Zugaib M, Bunduki V, Herman A (2010) Model predicted performance of second trimester Down syndrome screening with ultrasound prenasal thickness. J Ultrasound Med 29:1741–1747CrossRefGoogle Scholar
  13. 13.
    Miron J-P, Cuckle H, Miron P (2012) Prenasal thickness in first-trimester screening for Down syndrome. Prenat Diagn 32:695–697CrossRefGoogle Scholar
  14. 14.
    Manegold-Brauer G, Bourdil L, Berg C, Schoetzau A, Gembruch U, Geipel A (2015) Prenasal thickness to nasal bone length ratio in normal and trisomy 21 fetuses at 11–14 weeks of gestation. Prenat Diagn 35:1079–1084CrossRefGoogle Scholar
  15. 15.
    Bakker M, Pace M, de Jong-Pleij E, Birnie E, Kagan KO, Bilardo CM (2018) Prenasal thickness, prefrontal space ratio and other facial profile markers in first-trimester fetuses with aneuploidies, cleft palate, and micrognathia. Fetal Diagn Ther 43(3):231–240CrossRefGoogle Scholar
  16. 16.
    Maymon R, Ushakov F, Waisman D, Cuckle H, Tovbin E, Herman A (2006) A model for second-trimester Down's syndrome sonographic screening based on facial landmarks and digit length measurement. Ultrasound Obstet Gynecol 27:290–295CrossRefGoogle Scholar
  17. 17.
    Maymon R, Moskovitch M, Levinsohn-Tavor O, Weinraub Z, Herman A, Cuckle H (2009) Bed side estimation of Down's syndrome risk from second trimester ultrasound prenasal thickness. Ultrasound Obstet Gynecol 34:629–633CrossRefGoogle Scholar
  18. 18.
    Guis F, Ville Y, Vincent Y, Doumerc S, Pons JC, Frydman R (1995) Ultrasound evaluation of the fetal nasal bone throughout gestation. Ultrasound Obstet Gynecol 5:304–307CrossRefGoogle Scholar
  19. 19.
    Cicero S, Bindra R, Rembouskos G, Tripsanas C, Nicolaides KH (2002) Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11–14 weeks of gestation. J Matern Fetal Neonatal Med 11:400–402Google Scholar
  20. 20.
    Tovbin J, Tovbin L, Dreazen E, Bukovsky I, Herman A (2002) Prenatal age-specific reference intervals for measuring all five digits of the fetal hand. Ultrasound Obstet Gynecol 19:583–587CrossRefGoogle Scholar
  21. 21.
    Snijders RJM, Noble PL, Sebire NJ, Souka A, Nicolaides KH (1998) UK multicentre project on assessment of risk of trisomy 21 by maternal age and nuchal translucency thickness at 10–14 weeks of gestation. Lancet 352:343–346CrossRefGoogle Scholar
  22. 22.
    Kagan KO, Sonek J, Berg X, Berg C, Mallmann M, Abele H, Hoopmann M, Geipel A (2015) Facial markers in second and third trimester fetuses with trisomies 18 and 13, Triploidy and Turner syndrome. Ultrasound Obstet Gynecol 46:60–65CrossRefGoogle Scholar
  23. 23.
    Cuckle HS, Pergament EBP (2016) Multianalyte maternal serum screening for chromosomal abnormalities and neural tube defects. In: Milunsky EA, Milunsky J (eds) Genetic disorders and the fetus: diagnosis, prevention and treatment, 7th edn. Wiley-Blackwell, Hoboken, pp 483–540Google Scholar
  24. 24.
    Pandya PP, Altman DG, Brizot ML, Pettersen H, Nicolaides KH (1995) Repeatability of measurement of fetal nuchal translucency thickness. Ultrasound Obstet Gynecol 5:334–337CrossRefGoogle Scholar
  25. 25.
    Snijders RJ, Thom EA, Zachary JM, Platt LD, Greene N, Jackson LG, Sabbagha RE, Filkins K, Silver RK, Hogge WA, Ginsberg NA, Beverly S, Morgan P, Blum K, Chilis P, Hill LM, Hecker J, Wapner RJ (2002) First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique. Ultrasound Obstet Gynecol 19:353–359CrossRefGoogle Scholar
  26. 26.
    Logghe H, Cuckle H, Sehmi I (2003) Centre-specific ultrasound nuchal translucency medians needed for Down syndrome screening. Prenat Diagn 23:389–392CrossRefGoogle Scholar
  27. 27.
    Benacerraf BR, Gelman R, Frigoletto FD Jr (1987) Sonographic identification of second-trimester fetuses with Down's syndrome. N Engl J Med 317:1371–1376CrossRefGoogle Scholar
  28. 28.
    Vintzileos A, Walters C, Yeo L (2003) Absent nasal bone in the prenatal detection of fetuses with trisomy 21 in a high-risk population. Obstet Gynecol 101:905–908Google Scholar
  29. 29.
    Cuckle H (2001) Integrating antenatal Down's syndrome screening. Curr Opin Obstet Gynecol 13:175–181CrossRefGoogle Scholar
  30. 30.
    Benacerraf BR, Harlow BL, Frigoletto FD Jr (1990) Hypoplasia of the middle phalanx of the fifth digit. A feature of the second trimester fetus with Down's syndrome. J Ultrasound Med 9:389–394CrossRefGoogle Scholar
  31. 31.
    Geipel A, Gembruch U, Ludwig M, Germer U, Schwinger E, Dormeier A, Diedrich K (1999) Genetic sonography as the preferred option of prenatal diagnosis in women with pregnancies following intracytoplasmic sperm injection. Hum Reprod 14:2629–2634CrossRefGoogle Scholar
  32. 32.
    Kagan KO, Sonek J, Wagner P, Hoopmann M (2017) Principles of first trimester screening in the age of non-invasive prenatal diagnosis: screening for chromosomal abnormalities. Arch Gynecol Obstet 296:645–651CrossRefGoogle Scholar
  33. 33.
    Gil MM, Accurti V, Santacruz B et al (2017) Analysis of cell-free dna in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol 50:302–314CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Prenatal Medicine and Gynecologic UltrasoundUniversity of Basel, Women’s HospitalBaselSwitzerland
  2. 2.Department of Obstetrics and Gynecology, Institute of UltrasoundSackler School of Medicine, Assaf Harofeh Medical CentreTzrifinIsrael
  3. 3.Department of Obstetrics and Gynecology, Columbia University Medical CenterColumbia UniversityNew YorkUSA
  4. 4.Department of Obstetrics and Prenatal MedicineUniversity of BonnBonnGermany

Personalised recommendations