The Impact of Nasal Bone Reporting on Down Syndrome Prognosis: A Prospective Study
Abstract
Objectives: Accurate prenatal screening for Down syndrome (trisomy 21) is essential for effective maternal-fetal management. The nasal bone (NB) is a critical marker in first-trimester ultrasound assessments, yet reporting inconsistencies can affect prognostic outcomes. This study aims to investigate the impact of reporting the presence or absence of the nasal bone on Down syndrome prognosis in a cohort of pregnant women.
Methods: A prospective study was conducted involving women undergoing contingent prenatal screening during the first trimester. Participants with documented present NB were classified as having unknown NB, while those with unknown reports were treated as having present NB. The risk of Down syndrome was assessed using Benetech-PRA software, and all flagged cases were monitored postpartum to evaluate outcomes.
Results: Of the fetuses assessed, only 5% were diagnosed with Down syndrome. Approximately 7.3% of sonographers reported unknown NB, which was associated with a false-positive screening rate of 16±1%. The findings indicate that NB reporting significantly influences prognostic outcomes, particularly in cases where the NB status is unclear.
Conclusion: Accurate examination and reporting of the nasal bone are critical for reliable Down syndrome prognosis. Inadequate or incorrect NB assessment can lead to misleading results and increased false-positive rates in prenatal screening, underscoring the need for standardized reporting practices in ultrasound examinations.
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8. Spencer R HH, McCarthy L, Wimalasundera R, Pandya P. Non-invasive prenatal testing for aneuploidy screening. BMJ. 2020:371. .https://doi.org/10.1136/bmj.m3930.
9. Cicero S, Longo D, Rembouskos G, Sacchini C, Nicolaides KH. Absent nasal bone at 11-14 weeks of gestation and chromosomal defects. Ultrasound Obstet Gynecol. 2003;22(1):31-5.https://doi.org/10.1002/uog.170.
10. Aghaz F, Ojagh SZ, Khanjari S, Vaisi-Raygani A, Khazaei M, Bakhtiari M. The Contingent Prenatal Screening Test for Down's Syndrome and Neural Tube Defects in West of Iran. J Reprod Infertil. 2019;20(4):244-51
11. Shiefa S, Amargandhi M, Bhupendra J, Moulali S, Kristine T. First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome. Indian J Clin Biochem. 2013;28(1):3-12.https://doi.org/10.1007/s12291-012-0269-9.
12. A K. Maternal Serum Screening and Counselling. In: Down Syndrome Screening: A Practical Guide2024.https://doi.org//10.1007/978-981-99-7758-1_4.
13. Sagi-Dain L, Singer A, Ben Shachar S, Josefsberg Ben Yehoshua S, Feingold-Zadok M, Greenbaum L, et al. Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm. Obstet Gynecol. 2021;137(1):126-31.https://doi.org/10.1097/aog.0000000000004195.
14. Huang T, Wang FL, Boucher K, O'Donnell A, Rashid S, Summers AM. Racial differences in first trimester nuchal translucency. Prenat Diagn. 2007;27(12):1174-6.https://doi.org/10.1002/pd.1866.
15. Sevón E NH. False negatives in screening for chromosomal abnormalities2021.
16. Moreno-Cid M, Rubio-Lorente A, Rodríguez MJ, Bueno-Pacheco G, Tenías JM, Román-Ortiz C, et al. Systematic review and meta-analysis of performance of second-trimester nasal bone assessment in detection of fetuses with Down syndrome. Ultrasound Obstet Gynecol. 2014;43(3):247-53.https://doi.org/10.1002/uog.13228.
17. Ozcan T, Özlü T, Allen J, Peterson J, Pressman EK. Predictive role of prenasal thickness and nasal bone for Down syndrome in the second trimester. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):220-4.https://doi.org/10.1016/j.ejogrb.2013.08.039.
18. Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study. Lancet. 2001;358(9294):1665-7.https://doi.org/10.1016/s0140-6736(01)06709-5.
19. Orlandi F, Bilardo CM, Campogrande M, Krantz D, Hallahan T, Rossi C, 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(1):36-9.https://doi.org/10.1002/uog.167.
20. Das S, Sharma C, Yadav T, Dubey K, Shekhar S, Singh P, et al. Absent or hypoplastic nasal bone: What to tell the prospective parents? Birth Defects Res. 2024;116(5):e2348.https://doi.org/10.1002/bdr2.2348.
21. Kumar S, Selvakumar K. Various Methods for Computing Risk Factors of Down Syndrome in Fetus. Arch Computat Methods Eng. 2025;32(1):485-98.https://doi.org/10.1007/s11831-024-10158-8.
22. Dal Y, Akkuş F, Karagün Ş, Coşkun A. Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21. J Clin Ultrasound. 2024;52(4):368-76.https://doi.org/10.1002/jcu.23638.
23. Viora E, Errante G, Sciarrone A, Bastonero S, Masturzo B, Martiny G, et al. Fetal nasal bone and trisomy 21 in the second trimester. Prenat Diagn. 2005;25(6):511-5.https://doi.org/10.1002/pd.848.
24. Cicero S, Dezerega V, Andrade E, Scheier M, Nicolaides KH. Learning curve for sonographic examination of the fetal nasal bone at 11-14 weeks. Ultrasound Obstet Gynecol. 2003;22(2):135-7.https://doi.org/10.1002/uog.176.
25. Alldred SK, Takwoingi Y, Guo B, Pennant M, Deeks JJ, Neilson JP, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017;3(3):Cd012600.https://doi.org/10.1002/14651858.Cd012600.
26. Karim JN, Bradburn E, Roberts N, Papageorghiou AT. First-trimester ultrasound detection of fetal heart anomalies: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2022;59(1):11-25.https://doi.org/10.1002/uog.23740.
27. Liao Y, Wen H, Ouyang S, Yuan Y, Bi J, Guan Y, et al. Routine first-trimester ultrasound screening using a standardized anatomical protocol. Am J Obstet Gynecol. 2021;224(4):396.e1-.e15.https://doi.org/10.1016/j.ajog.2020.10.037.
28. Larose C, Massoc P, Hillion Y, Bernard JP, Ville Y. Comparison of fetal nasal bone assessment by ultrasound at 11-14 weeks and by postmortem X-ray in trisomy 21: a prospective observational study. Ultrasound Obstet Gynecol. 2003;22(1):27-30.https://doi.org/10.1002/uog.169.
29. Tørring N. First trimester combined screening - focus on early biochemistry. Scand J Clin Lab Invest. 2016;76(6):435-47.https://doi.org/10.1080/00365513.2016.1200131.
30. Korevaar TI, Steegers EA, de Rijke YB, Schalekamp-Timmermans S, Visser WE, Hofman A, et al. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study. Eur J Epidemiol. 2015;30(9):1057-66.https://doi.org/10.1007/s10654-015-0039-0.
31. Honarjoo M, Kohan S, Zarean E, Tarrahi MJ. Assessment of β-human-derived chorionic gonadotrophic hormone (βhCG) and pregnancy-associated plasma protein A (PAPP-A) levels as predictive factors of preeclampsia in the first trimester among Iranian women: a cohort study. BMC Pregnancy Childbirth. 2019;19(1):464.https://doi.org/10.1186/s12884-019-2526-x.
32. Spencer K, Heath V, El-Sheikhah A, Ong CYT, Nicolaides KH. Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations. Prenat Diagn. 2005;25(5):365-9.https://doi.org/10.1002/pd.1153.
33. Cicero S, Bindra R, Rembouskos G, Spencer K, Nicolaides KH. Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency, absent fetal nasal bone, free beta-hCG and PAPP-A at 11 to 14 weeks. Prenat Diagn. 2003;23(4):306-10.https://doi.org/10.1002/pd.588.
34. Abele H, Lüthgens K, Hoopmann M, Kagan KO. Impact of the maternal age-related risk in first-trimester combined screening for trisomy 21. Fetal Diagn Ther. 2011;30(2):135-40.https://doi.org/10.1159/000327157.
2. Bull MJ, Trotter T, Santoro SL, Christensen C, Grout RW, GENETICS TCO. Health Supervision for Children and Adolescents With Down Syndrome. Pediatrics. 2022;149(5).https://doi.org/10.1542/peds.2022-057010.
3. LeFevre NM, Sundermeyer RL. Fetal Aneuploidy: Screening and Diagnostic Testing. Am Fam Physician. 2020;101(8):481-8.
4. Ozdemir S, Sahin O, Acar Z, Demir GZ, Ermin E, Aydin A. Prediction of Pregnancy Complications With Maternal Biochemical Markers Used in Down Syndrome Screening. Cureus. 2022;14(3):e23115.https://doi.org/10.7759/cureus.23115.
5. Wagner P, Sonek J, Klein J, Hoopmann M, Abele H, Kagan KO. First-trimester ultrasound screening for trisomy 21 based on maternal age, fetal nuchal translucency, and different methods of ductus venosus assessment. Prenat Diagn. 2017;37(7):680-5.https://doi.org/10.1002/pd.5065.
6. Wojda KM, Moczulska H, Sieroszewski PJ. The absence of fetal nasal bones in ultrasound examination between 11 + 0 and 13 + 6 weeks of gestation versus the occurrence of trisomies 21, 18, and 13. Ginekol Pol. 2019;90(10):604-6.https://doi.org/10.5603/gp.2019.0104.
7. Sonek JD, Cicero S, Neiger R, Nicolaides KH. Nasal bone assessment in prenatal screening for trisomy 21. Am J Obstet Gynecol. 2006;195(5):1219-30.https://doi.org/10.1016/j.ajog.2005.11.042.
8. Spencer R HH, McCarthy L, Wimalasundera R, Pandya P. Non-invasive prenatal testing for aneuploidy screening. BMJ. 2020:371. .https://doi.org/10.1136/bmj.m3930.
9. Cicero S, Longo D, Rembouskos G, Sacchini C, Nicolaides KH. Absent nasal bone at 11-14 weeks of gestation and chromosomal defects. Ultrasound Obstet Gynecol. 2003;22(1):31-5.https://doi.org/10.1002/uog.170.
10. Aghaz F, Ojagh SZ, Khanjari S, Vaisi-Raygani A, Khazaei M, Bakhtiari M. The Contingent Prenatal Screening Test for Down's Syndrome and Neural Tube Defects in West of Iran. J Reprod Infertil. 2019;20(4):244-51
11. Shiefa S, Amargandhi M, Bhupendra J, Moulali S, Kristine T. First Trimester Maternal Serum Screening Using Biochemical Markers PAPP-A and Free β-hCG for Down Syndrome, Patau Syndrome and Edward Syndrome. Indian J Clin Biochem. 2013;28(1):3-12.https://doi.org/10.1007/s12291-012-0269-9.
12. A K. Maternal Serum Screening and Counselling. In: Down Syndrome Screening: A Practical Guide2024.https://doi.org//10.1007/978-981-99-7758-1_4.
13. Sagi-Dain L, Singer A, Ben Shachar S, Josefsberg Ben Yehoshua S, Feingold-Zadok M, Greenbaum L, et al. Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm. Obstet Gynecol. 2021;137(1):126-31.https://doi.org/10.1097/aog.0000000000004195.
14. Huang T, Wang FL, Boucher K, O'Donnell A, Rashid S, Summers AM. Racial differences in first trimester nuchal translucency. Prenat Diagn. 2007;27(12):1174-6.https://doi.org/10.1002/pd.1866.
15. Sevón E NH. False negatives in screening for chromosomal abnormalities2021.
16. Moreno-Cid M, Rubio-Lorente A, Rodríguez MJ, Bueno-Pacheco G, Tenías JM, Román-Ortiz C, et al. Systematic review and meta-analysis of performance of second-trimester nasal bone assessment in detection of fetuses with Down syndrome. Ultrasound Obstet Gynecol. 2014;43(3):247-53.https://doi.org/10.1002/uog.13228.
17. Ozcan T, Özlü T, Allen J, Peterson J, Pressman EK. Predictive role of prenasal thickness and nasal bone for Down syndrome in the second trimester. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):220-4.https://doi.org/10.1016/j.ejogrb.2013.08.039.
18. Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11-14 weeks of gestation: an observational study. Lancet. 2001;358(9294):1665-7.https://doi.org/10.1016/s0140-6736(01)06709-5.
19. Orlandi F, Bilardo CM, Campogrande M, Krantz D, Hallahan T, Rossi C, 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(1):36-9.https://doi.org/10.1002/uog.167.
20. Das S, Sharma C, Yadav T, Dubey K, Shekhar S, Singh P, et al. Absent or hypoplastic nasal bone: What to tell the prospective parents? Birth Defects Res. 2024;116(5):e2348.https://doi.org/10.1002/bdr2.2348.
21. Kumar S, Selvakumar K. Various Methods for Computing Risk Factors of Down Syndrome in Fetus. Arch Computat Methods Eng. 2025;32(1):485-98.https://doi.org/10.1007/s11831-024-10158-8.
22. Dal Y, Akkuş F, Karagün Ş, Coşkun A. Comparison of the ratio of second trimester fetal biometric measurements to fetal nasal bone length in fetuses with normal karyotype and trisomy 21. J Clin Ultrasound. 2024;52(4):368-76.https://doi.org/10.1002/jcu.23638.
23. Viora E, Errante G, Sciarrone A, Bastonero S, Masturzo B, Martiny G, et al. Fetal nasal bone and trisomy 21 in the second trimester. Prenat Diagn. 2005;25(6):511-5.https://doi.org/10.1002/pd.848.
24. Cicero S, Dezerega V, Andrade E, Scheier M, Nicolaides KH. Learning curve for sonographic examination of the fetal nasal bone at 11-14 weeks. Ultrasound Obstet Gynecol. 2003;22(2):135-7.https://doi.org/10.1002/uog.176.
25. Alldred SK, Takwoingi Y, Guo B, Pennant M, Deeks JJ, Neilson JP, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017;3(3):Cd012600.https://doi.org/10.1002/14651858.Cd012600.
26. Karim JN, Bradburn E, Roberts N, Papageorghiou AT. First-trimester ultrasound detection of fetal heart anomalies: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2022;59(1):11-25.https://doi.org/10.1002/uog.23740.
27. Liao Y, Wen H, Ouyang S, Yuan Y, Bi J, Guan Y, et al. Routine first-trimester ultrasound screening using a standardized anatomical protocol. Am J Obstet Gynecol. 2021;224(4):396.e1-.e15.https://doi.org/10.1016/j.ajog.2020.10.037.
28. Larose C, Massoc P, Hillion Y, Bernard JP, Ville Y. Comparison of fetal nasal bone assessment by ultrasound at 11-14 weeks and by postmortem X-ray in trisomy 21: a prospective observational study. Ultrasound Obstet Gynecol. 2003;22(1):27-30.https://doi.org/10.1002/uog.169.
29. Tørring N. First trimester combined screening - focus on early biochemistry. Scand J Clin Lab Invest. 2016;76(6):435-47.https://doi.org/10.1080/00365513.2016.1200131.
30. Korevaar TI, Steegers EA, de Rijke YB, Schalekamp-Timmermans S, Visser WE, Hofman A, et al. Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study. Eur J Epidemiol. 2015;30(9):1057-66.https://doi.org/10.1007/s10654-015-0039-0.
31. Honarjoo M, Kohan S, Zarean E, Tarrahi MJ. Assessment of β-human-derived chorionic gonadotrophic hormone (βhCG) and pregnancy-associated plasma protein A (PAPP-A) levels as predictive factors of preeclampsia in the first trimester among Iranian women: a cohort study. BMC Pregnancy Childbirth. 2019;19(1):464.https://doi.org/10.1186/s12884-019-2526-x.
32. Spencer K, Heath V, El-Sheikhah A, Ong CYT, Nicolaides KH. Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations. Prenat Diagn. 2005;25(5):365-9.https://doi.org/10.1002/pd.1153.
33. Cicero S, Bindra R, Rembouskos G, Spencer K, Nicolaides KH. Integrated ultrasound and biochemical screening for trisomy 21 using fetal nuchal translucency, absent fetal nasal bone, free beta-hCG and PAPP-A at 11 to 14 weeks. Prenat Diagn. 2003;23(4):306-10.https://doi.org/10.1002/pd.588.
34. Abele H, Lüthgens K, Hoopmann M, Kagan KO. Impact of the maternal age-related risk in first-trimester combined screening for trisomy 21. Fetal Diagn Ther. 2011;30(2):135-40.https://doi.org/10.1159/000327157.
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| Issue | Vol 3 No 3 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| Contingent prenatal screening test Down syndrome Nasal bone Trisomy 21 | ||
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How to Cite
1.
Rahnama M, Manzoury A, Rashidmehr N, Ghasemzadeh N, Mojarrad M. The Impact of Nasal Bone Reporting on Down Syndrome Prognosis: A Prospective Study. ABI. 2025;3(3):189-196.
