First-Trimester Detection of Down Syndrome Using Fetal Ultrasound Markers Form

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM

EFFECTIVE DATE: 11|17|2005 POLICY LAST REVIEWED: 07|16|2025

OVERVIEW Ultrasound (US) markers can potentially increase the sensitivity of biochemical measures for first-trimester detection of Down syndrome. Nuchal translucency (NT) refers to the US detection of subcutaneous edema in the fetal neck between weeks 10 and 13 of gestation. Fetal nasal bone examination involves US assessment at 11 to 14 weeks of gestation to identify the presence or absence of the nasal bone.

Note: This policy only addresses the US markers nuchal translucency and fetal nasal bone assessment.

MEDICAL CRITERIA Not applicable

PRIOR AUTHORIZATION
Not applicable

POLICY STATEMENT Medicare Advantage Plans and Commercial Products First-trimester screening for detection of Down syndrome incorporating maternal serum markers and measurement of fetal nuchal translucency may be considered medically necessary for women who are adequately counseled and desire information on the risk of having a child with Down syndrome.

First-trimester screening for detection of Down syndrome using measurement of nuchal translucency alone is not covered for Medicare Advantage Plans and not medically necessary for Commercial products as the evidence is insufficient to determine the effects of the technology on health outcomes.

First-trimester screening for detection of Down syndrome incorporating fetal nasal bone assessment translucency is not covered for Medicare Advantage Plans and not medically necessary for Commercial products as the evidence is insufficient to determine the effects of the technology on health outcomes.

COVERAGE Benefits may vary between groups/contracts. Please refer to the appropriate member Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for applicable radiology benefits/coverage.

BACKGROUND Definitive diagnosis of Down syndrome and other chromosomal abnormalities requires amniocentesis or chorionic villus sampling, both of which are invasive procedures that carry a risk of miscarriage estimated at 0.5% to 1%. Because of this risk, before biochemical screening existed, diagnosis was generally only offered to women aged 35 years or older, for whom the risk of the procedure approximated the risk of Down syndrome. However, most babies with Down syndrome are born from mothers younger than 35 years, even though the mothers are at lower individual risk. This situation created interest in developing less invasive screening programs based on assessment of serum markers that have shown associations with Down syndrome. In the late 1980s, biochemical screening at 16 weeks of gestation was developed and began to be offered to all pregnant women. Biochemical screening consists of maternal serum measurements
α-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol (ie, triple screen). More recently, a fourth marker has been used, inhibin-A (quadruple screen). The triple screen identifies approximately 69% of Down syndrome pregnancies and the quadruple screen 81%, both at a 5%
Medical Coverage Policy | First-Trimester Detection of Down Syndrome Using Fetal Ultrasound Markers

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

false-positive rate. This false-positive rate refers to the proportion of all tests administered that are falsely positive at the cutoff point that produces that particular value of sensitivity. Among women who test positive, only about 2% actually have a fetus with Down syndrome.

There has been interest in Ultrasound (US) markers to improve the accuracy of biochemical screening. One potential marker is fetal NT. This refers to the US detection of subcutaneous edema in the fetal neck and is measured as the maximal thickness of the sonolucent zone between the inner aspect of the fetal skin and the outer aspect of the soft tissue overlying the cervical spine or the occipital bone. In the early 1990s, screening studies of pregnant women reported an association between increased NT in the first trimester of pregnancy (10-13 weeks of gestation) and chromosomal defects, most commonly Down syndrome (trisomy 21), but also trisomy 18 and 13. NT could be done alone as a first-trimester screen or in combination with maternal serum markers, free beta subunit of hCG and pregnancy-associated plasma protein-A. These serum markers differ from those used in the second-trimester triple or quadruple screen.

Another potential US marker is fetal nasal bone examination. The technique for assessing the nasal bone is to view the fetal face longitudinally and exactly in the midline. The nasal bone synostosis resembles a thin echogenic line within the bridge of the nose. The nasal bones are considered to be present if this line is more echogenic than the overlying skin and absent if the echogenicity is the same or less than the skin, or if it is not visible. The absence of fetal nasal bone is considered to be a positive test result, indicating an increased risk of Down syndrome. In some cases, the sonographer will not be able to visualize the nasal area of the fetus’s face and thus cannot make a determination of the presence or absence of nasal bone. The inability to visualize the nasal bone is regarded as an unsuccessful examination, rather than a positive test result. Fetal nasal bone examination can be done from 11 weeks to just before 14 weeks of gestation. It is sometimes recommended that, if the nasal bone is absent on US done between 11 and 12 weeks of gestation, a second examination be done 2 weeks later. Fetal nasal bone assessment can be done along with NT, or in the second step of a 2- stage screen for cases that are borderline using other first-trimester markers.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of maternal serum markers and nuchal translucency, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. There is sufficient evidence from 2 large multicenter prospective studies the Serum, Urine, and Ultrasound Screening Study (SURUSS) and the First and Second Trimester Evaluation of Risk (FASTER) trials well as several smaller studies, that first-trimester screening for Down syndrome with measurement of fetal nuchal translucency (NT) and maternal serum markers is at least as accurate as alternative tests and may allow earlier confirmation or exclusion of Down syndrome. The evidence is sufficient to determine qualitatively that the technology results in a meaningful improvement in the net health outcome.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of nuchal translucency alone, the evidence includes observational screening studies. Relevant outcomes are test accuracy and validity and resource utilization. The large multicenter prospective studies SURUSS and FASTER found, overall, that first-trimester screening with NT alone is inferior to first or second-trimester combined screening. Additional testing may not be necessary in those few cases when NT is at least 4.0 mm due to the high likelihood of Down syndrome, but this would affect only a very small number of cases (0.09%-0.3%). The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who are pregnant and in the first trimester who receive first-trimester Down syndrome screening of fetal nasal bone, the evidence includes several observational studies. Relevant outcomes are test accuracy and validity and resource utilization. The accuracy of testing in the published literature is variable, with some studies reporting relatively low sensitivity rates. The variability in accuracy reported may reflect the difficulty in performing and interpreting this test, and test results are likely prone to differences in operator characteristics. Limited evidence has suggested that there may be modest incremental benefit when the test is used in combination with NT measurement and serum markers, but the degree of benefit is unclear. The evidence is insufficient to determine the effects of the technology on health outcomes.

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 3 (401) 274-4848 WWW.BCBSRI.COM

CODING Medicare Advantage Plans and Commercial Products The following CPT code(s) are covered if the conditions cited above are met: 76813 Ultrasound, pregnant uterus, real time with image documentation, first trimester fetal

         nuchal translucency measurement, transabdominal or transvaginal approach; single or first gestation

76814 Ultrasound, pregnant uterus, real time with image documentation, first trimester fetal

         nuchal translucency measurement, transabdominal or transvaginal approach; each 
         additional gestation (List separately in addition to code for primary procedure)

There is no specific CPT code(s) for ultrasound assessment of fetal bone translucency. It should be reported with an unlisted code.

RELATED POLICIES Unlisted Procedures

PUBLISHED Provider Update, September 2025 Provider Update, September 2024 Provider Update, April 2023 Provider Update, June 2022 Provider Update, May 2021

REFERENCES

1. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. Jan 2007;109(1):217-227. PMID 17197615
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3. Wald NJ, Rodeck C, Hackshaw AK, et al. First and second trimester antenatal screening for Down's syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS). J Med Screen. 2003;10(2):56-104. PMID 14746340
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11. Berktold L, C VK, Hillemanns P, et al. Analysis of the impact of PAPP-A, free beta-hCG and nuchal translucency thickness on the advanced first trimester screening. Arch Gynecol Obstet. Mar 2013;287(3):413-420. PMID 23080546
12. Peuhkurinen S, Laitinen P, Honkasalo T, et al. Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland. Acta Obstet Gynecol Scand. Jul 2013;92(7):769-774. PMID 23369035
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500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 4 (401) 274-4848 WWW.BCBSRI.COM

14. Kagan KO, Staboulidou I, Cruz J, et al. Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing. Ultrasound Obstet Gynecol. Nov 2010;36(5):542-547. PMID 20503223 15. Baer RJ, Flessel MC, Jelliffe-Pawlowski LL, et al. Detection rates for aneuploidy by first- trimester and sequential screening. Obstet Gynecol. Oct 2015;126(4):753-759. PMID 26348180
15. Baer RJ, Flessel MC, Jelliffe-Pawlowski LL, et al. Detection rates for aneuploidy by first-trimester and sequential screening. Obstet Gynecol. Oct 2015;126(4):753-759. PMID 26348180
16. Wald NJ, Huttly WJ, Murphy KW, et al. Antenatal screening for Down's syndrome using the Integrated test at two London hospitals. J Med Screen. 2009;16(1):7-10. PMID 19349524
17. Torella M, Tormettino B, Zurzolo V, et al. Screening for trisomy 21 by maternal age fetal nuchal translucency thickness and maternal serum sample. Minerva Ginecol. Dec 2013;65(6):653-659. PMID 23881389 18. Comstock CH, Malone FD, Ball RH, et al. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening? Am J Obstet Gynecol. Sep 2006;195(3):843-847. PMID 16949423
18. Comstock CH, Malone FD, Ball RH, et al. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening? Am J Obstet Gynecol. Sep 2006;195(3):843-847. PMID 16949423
19. Miron P, Cote YP, Lambert J. Nuchal translucency thresholds in prenatal screening for Down syndrome and trisomy 18. J Obstet Gynaecol Can. Mar 2009;31(3):227-235. PMID 19416569
20. Fetal Medicine Foundation website. Certificate of Competence in the Measurement of Nuchal Translucency. . https://fetalmedicine.org/nuchal-translucency-scan. Accessed March 6, 2015.
21. Fetal Medicine Foundation website. http://www.fetalmedicineusa.com/. Accessed July 22, 2016.
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23. Schmidt P, Staboulidou I, Elsasser M, et al. How imprecise may the measurement of fetal nuchal translucency be without worsening first-trimester screening? Fetal Diagn Ther. 2008;24(3):291-295. PMID 18818502
24. Rosen T, D'Alton ME, Platt LD, et al. First-trimester ultrasound assessment of the nasal bone to screen for aneuploidy. Obstet Gynecol. Aug 2007;110(2 Pt 1):399-404. PMID 17666617
25. Malone FD, Ball RH, Nyberg DA, et al. First-trimester nasal bone evaluation for aneuploidy in the general population. Obstet Gynecol. Dec 2004;104(6):1222-1228. PMID 15572480
26. Sonek JD, Cicero S, Neiger R, et al. Nasal bone assessment in prenatal screening for trisomy 21. Am J Obstet Gynecol. Nov 2006;195(5):1219-1230. PMID 16615922
27. Prefumo F, Sairam S, Bhide A, et al. First-trimester nuchal translucency, nasal bones, and trisomy 21 in selected and unselected populations. Am J Obstet Gynecol. Mar 2006;194(3):828-833. PMID 16522420
28. Chanprapaph P, Dulyakasem C, Phattanchindakun B. Sensitivity of multiple first trimester sonomarkers in fetal aneuploidy detection. J Perinat Med. May 2015;43(3):359-365. PMID 25222592
29. Cicero S, Avgidou K, Rembouskos G, et al. Nasal bone in first-trimester screening for trisomy 21. Am J Obstet Gynecol. Jul 2006;195(1):109-114. PMID 16813749
30. Sahota DS, Leung TY, Chan LW, et al. Comparison of first-trimester contingent screening strategies for Down syndrome. Ultrasound Obstet Gynecol. Mar 2010;35(3):286-291. PMID 20052660
31. Hsiao CH, Cheng PJ, Shaw SW, et al. Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: a five-year prospective study. Fetal Diagn Ther. Feb 6 2014;35(4):296-301. PMID 24503519
32. Adiego B, Martinez-Ten P, Illescas T, et al. First-trimester assessment of nasal bone using retro nasal triangle view: a prospective study. Ultrasound Obstet Gynecol. 2014;43(3):272-276. PMID 23733531
33. Nanni M, Maroni E, Bevini M, et al. The usefulness of volume NT software in measuring the fetal nasal bone at 11 to 13 + 6 weeks of gestation. Prenat Diagn. May 2014;34(5):500-504. PMID 24510896
34. Audibert F, Gagnon A, Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada, et al. Prenatal screening for and diagnosis of aneuploidy in twin pregnancies. J Obstet Gynaecol Can. Jul 2011;33(7):754-767. PMID 21749753
35. ACOG Committee on Practice Bulletins. Screening for Fetal Aneuploidy (No. 163). www.acog.org. Accessed July, 2016.

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 5 (401) 274-4848 WWW.BCBSRI.COM

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