Antenatal features of Down syndrome
Antenatal screening of Down syndrome (and other less common aneuploidies) should be available as a routine component of antenatal care. It allows families to either adjust to the idea of having a child with the condition or to consider termination of pregnancy.
There is a strong association between the incidence of Down syndrome and maternal age. Background risk based on maternal age is incorporated into both the serum screening based risk calculations and into the calculation of increased risk in the presence of a soft marker in 2nd trimester (see below).
Specific data to follow
Maternal serum screening
Please refer to the antenatal screening for a general discussion of the avenues of screening and diagnosis in the antenatal period.
Combined serum screening has an approximately 85% detection rate, with 5% false positive rate 8.
Serological markers: MSS1
- maternal beta hCG
- higher than chromosomally normal fetuses
- difference increases with gestation
- lower than chromosomally normal fetuses
- difference decreases with gestation: therefore not commonly used as a second-trimester test
A triple screening / quadruple screening is done in high-risk cases. However combined screening test is most preferred. Detection rate for trisomy 21 is at approximately 80% with a false positive rate of ~5% 8.
Serological markers: MSS2
- maternal free beta-hCG: higher than chromosomally normal fetuses
- inhibin A: higher than chromosomally normal fetuses
- AFP: lower than chromosomally normal fetuses
- unconjugated oestriol (uE3): lower than chromosomally normal fetuses
Nuchal translucency: thickness depends on the size of the fetus (CRL), but in general it is considered abnormal if >3 mm.
There is evidence that the inclusion of nasal bone measurement improves the specificity of 1st trimester data 5.
Ductus venosus flow is another parameter that has been reported to further increase the sensitivity of 1st trimester screening 12.
Approximately 30% of babies with Down syndrome have detectable abnormalities on the mid-trimester ultrasound 1.
Soft markers are sonographic findings that do not in themselves cause any adverse outcomes. However, they are seen more frequently in fetuses with an abnormality. This article addresses the soft markers that are specific to Down syndrome. For a general discussion, please refer to the article on soft markers.
In the presence of a soft marker, the risk of Down syndrome is recalculated as: new risk = baseline risk x likelihood ratio (LR).
nuchal fold thickness > 6 mm
- likelihood ratio: 17 1
hypoplastic nasal bone
- has emerged in recent years as a particularly strong marker
- absence of a nasal bone has a likelihood ratio of 83 1
echogenic intracardiac focus
- likelihood ratio: 1.5 1
- likelihood ratio: 6.1
- likelihood ratio: 7.5
- likelihood ratio: 2.7
single umbilical artery
- only considered a soft marker if other abnormalities are present
- in an otherwise normal 2nd trimester ultrasound it is not a marker of aneuploidy
- weak association with aneuploidy
The following may be present in association with Down syndrome:
- cardiac defects
- central nervous system
Other features that may be present, but are neither a structural abnormality or a validated soft marker 8
- hypoplastic 5th digit
- wide iliac angle
- shortened frontothalamic distance
- short fetal ear length
Some fetuses can develop transient abnormal myelopoiesis (TAM) particularly towards the 3rd trimester and can then develop fetal hepatomegaly 11.
- 1. Bethune M. Literature review and suggested protocol for managing ultrasound soft markers for Down syndrome: thickened nuchal fold, echogenic bowel, shortened femur, shortened humerus, pyelectasis and absent or hypoplastic nasal bone. Australas Radiol. 2007;51 (3): 218-25. doi:10.1111/j.1440-1673.2007.01713.x - Pubmed citation
- 2. Saller DN, Canick JA. Current methods of prenatal screening for Down syndrome and other fetal abnormalities. Clin Obstet Gynecol. 2008;51 (1): 24-36. doi:10.1097/GRF.0b013e318160f274 - Pubmed citation
- 3. Smith-bindman R, Hosmer W, Feldstein VA et-al. Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA. 2001;285 (8): 1044-55. doi:10.1001/jama.285.8.1044 - Pubmed citation
- 4. Cicero S, Spencer K, Avgidou K et-al. Maternal serum biochemistry at 11-13(+6) weeks in relation to the presence or absence of the fetal nasal bone on ultrasonography in chromosomally abnormal fetuses: an updated analysis of integrated ultrasound and biochemical screening. Prenat. Diagn. 2005;25 (11): 977-83. doi:10.1002/pd.1211 - Pubmed citation
- 5. Kagan KO, Cicero S, Staboulidou I et-al. Fetal nasal bone in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound Obstet Gynecol. 2009;33 (3): 259-64. doi:10.1002/uog.6318 - Pubmed citation
- 6. Maiz N, Valencia C, Kagan KO et-al. Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound Obstet Gynecol. 2009;33 (5): 512-7. doi:10.1002/uog.6330 - Pubmed citation
- 7. Aitken DA, Wallace EM, Crossley JA et-al. Dimeric inhibin A as a marker for Down's syndrome in early pregnancy. N. Engl. J. Med. 1996;334 (19): 1231-6. doi:10.1056/NEJM199605093341904 - Pubmed citation
- 8. Rumack CM, Wilson SR, Charboneau JW. Diagnostic ultrasound. Mosby. (2005) ISBN:0323020232. Read it at Google Books - Find it at Amazon
- 9. Woodward PJ. Diagnostic imaging, Obstetrics. Amirsys. (2005) ISBN:1416023356. Read it at Google Books - Find it at Amazon
- 10. Tennstedt C, Chaoui R, Körner H et-al. Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study. Heart. 1999;82 (1): 34-9. doi:10.1136/hrt.82.1.34 - Free text at pubmed - Pubmed citation
- 11. Hamada H, Yamada N, Watanabe H et-al. Hypoechoic hepatomegaly associated with transient abnormal myelopoiesis provides clues to trisomy 21 in the third-trimester fetus. Ultrasound Obstet Gynecol. 2001;17 (5): 442-4. doi:10.1046/j.1469-0705.2001.00362.x - Pubmed citation
- 12. Florjański J, Fuchs T, Zimmer M, Homola W, Pomorski M, Blok D. The role of ductus venosus Doppler flow in the diagnosis of chromosomal abnormalities during the first trimester of pregnancy. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 22 (3): 395-401. Pubmed