BlueCross BlueShield of Tennessee Medical Policy Manual

First-Trimester Detection of Down Syndrome Using Fetal Ultrasound Markers Combined with Maternal Serum Assessment


Definitive diagnosis of Down syndrome and other chromosomal abnormalities requires amniocentesis or chorionic villus sampling (CVS), both of which are invasive procedures that carry a risk of miscarriage estimated at 0.5% to 1%. Less invasive screening programs have been developed with the use of biochemical markers that show an association with Down syndrome.

The May 2016 American College of Obstetricians and Gynecologists  recommendation for first trimester screening for fetal abnormalities includes a nuchal translucency (ultrasound detection of subcutaneous edema in the fetal neck), serum free beta subunit of human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). A specific risk estimate is calculated using these results as well as maternal factors such as maternal age, prior history, weight, race, and number of fetuses. Combined screening shows an 82% to 87% predictability rating when done in the first trimester. Measurement of nuchal translucency alone is less effective for first-trimester screening than the combined testing. 

Another potential ultrasound marker is fetal nasal bone examination. The technique for assessing the nasal bone using ultrasound involves viewing the fetal face longitudinally and exactly in the midline. The nasal bones are considered to be present if the line within the bridge of the nose 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.





This policy does not address the second trimester maternal markers which measure alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol (i.e., triple screen) or the addition of a fourth marker, inhibin-A (quadruple screen).

There is insufficient evidence on the performance of fetal nasal bone assessment to determine its impact on health outcomes.  Additional studies are needed before conclusions can be drawn about its utility.


American College of Obstetricians and Gynecologists, Committee on Genetics; Society of Maternal-Fetal Medicine. (2015, September). Cell-free DNA Screening for fetal aneuploidy. committee opinion number 640. Retrieved August 7, 2015 from:

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 162. (2016, May) Prenatal diagnostic testing for genetic disorders. Retrieved November 22, 2016 from:

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 163. (2016, May) Screening for fetal aneuploidy. Retrieved November 22, 2016 from:

Hsiao, C., Cheng, P., Shaw, S., Hsu, J., Chen, R., Tseng, Y., et. al. (2014) Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: a five-year prospective study. Fetal Diagnostic Theory. 2014;35(4):296-301. Abstract retrieved November 22, 2016 from PubMed database.

Kagan, K. O., Staboulidou, I., Cruz, J., Wright, D., & Nicolaides, K. H. (2010). Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing. Ultrasound in Obstetrics & Gynecology, 36 (5), 542-547. (Level 3 evidence)

Kim, S., & Jun, J. (2013). Simplified protocol of nuchal translucency measurement. Is it still effective? Obstetrics and Gynecology Science. 56 (5), 307-311. (Level 3 evidence)

Liu, Y., Ye, X., Zhang, N., Zhang, B., Guo, C., Huang, W., Jing, L., et al. (2015). Diagnostic value of ultrasonographic combining biochemical markers for Down syndrome screening in first trimester: a meta-analysis. Prenatal Diagnosis, 35 (9), 879-887. Abstract retrieved November 12, 2015 from PubMed database.

National Institute for Health and Clinical Excellence. (2017, January). Clinical guideline: antenatal care for uncomplicated pregnancies. Retrieved November 8, 2017 from

Prats, P., Rodriguez, I., Comas, C., & Puerto, B. (2014). Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: a meta-analysis. Prenatal Diagnosis, 34 (11), 1077-1083. Abstract retrieved November 12, 2015 from PubMed database.

Sahota, D. S., Leung, T. Y., Chan, L. W., Law, L. W., Fung, T. Y., Chen, M., & Lau, T. K. (2010). Comparison of first-trimester contingent screening strategies for Down syndrome. Ultrasound in Obstetrics & Gynecology, 35 (3), 286-291. (Level 4 evidence)




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