Hilary HochbergGillian Lieberman, MD

Hilary HochbergAdvanced Radiology Clerkship

Dr. Gillian Lieberman

Down’s Syndrome: Ultrasound Screening

October 2001

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Hilary HochbergGillian Lieberman, MD

Patient M.C.

• 32 year old female presents at 16 weeks gestational age with “abnormal triple screen test”

• Obstetrician referred M.C. for ultrasound evaluation to look for signs of Down’s syndrome or other congenital anomalies.

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Hilary HochbergGillian Lieberman, MD

Screening for Down syndrome by maternal serum markers:

THE TRIPLE SCREENAFP HcG UE3

Absolute 58 ng/ml 97.36 ju/ml 28 ng/ml

Relative 1.93 MoM 3.12 MoM 0.42 MoM

Pt M.C.

Trisomy 21

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Hilary HochbergGillian Lieberman, MD

http://www.fetalmedicine.com/11-14scanbook/Figures/fig01-04.htm

Maternal age-related risk for chromosomal abnormalities

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Hilary HochbergGillian Lieberman, MD

Prevalence of trisomy 21 by maternal age and gestational age

Snijders RJM, Sundberg K, Holzgreve W, Henry G, Nicolaides KH. Maternal age and gestation- specific risk for trisomy 21. Ultrasound Obstet Gynecol 1999;13:167–70

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Hilary HochbergGillian Lieberman, MD

Ultrasound Screening of Down’s Syndrome

•Trisomy 21: Most common chromosomal abnormalityAverage incidence 1:800 live births

•Current second-trimester ultrasound screening detectsup to 60% of Down’s syndrome fetuses*

•Helpful to correlate a large number of relatively nonspecific visual and biometric markers

•Ideally, perform at age when confirmatory diagnosis can be made, safe termination can be offered

Image:http://anatomy.med.unsw.edu.au/cbl/embryo/sysnote.htm

*Chitty LS: Antenatal screening for aneuploidy. Curr Opin Obstet Gynecol 10:91,1998.

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Hilary HochbergGillian Lieberman, MD

Trisomy 21

Trisomy 18

Trisomy 13 Triploidy Turner

Skull/brain Strawberry-shaped head BrachycephalyMicrocephalyVentriculomegalyHoloprosencephalyChoroid plexus cysts Absent corpus callosumPosterior fossa cyst Enlarged cisterna magna

–+ –+ –+ –+ +

+ + –+ –+ + + +

–+ + –+ ––+ +

–––+ –––––

–+ + ––––––

Face/neckFacial cleft MicrognathiaNuchal edemaCystic hygromata

––+ –

+ + + –

+ –+ –

–+ ––

–––+

ChestDiaphragmatic hernia Cardiac abnormality

–+

+ +

+ +

–+

–+

AbdomenExomphalos Duodenal atresia Collapsed stomach Mild hydronephrosisOther renal abnormalities

–+ + + +

+ –+ + +

+ ––+ +

––––+

–––+ –

OtherHydrops Small for gestational age Relatively short femur Clinodactyly Overlapping fingers Polydactyly Syndactyly Talipes

+ –+ + ––––

–+ + –+ ––+

–––––+ –+

–+ + –––+ +

+ + + –––––

Sonographic finding

Pilu G, Nicolaides KH. Diagnosis of fetal abnormalities. The 18-23 week scan. The Parthenon Publishing Group: New York, 1999.

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Hilary HochbergGillian Lieberman, MD

http://www.fetalmedicine.com/nuchal.htm

Unclear physiological basis of fluid accumulation1. Increased risk of associated cardiac abnormalities2. Increased hyaluronanidase in ECM

Nuchal translucency > 3mm abnormal

NUCHAL TRANSLUCENCY: 1st Trimester

Most clinically useful marker for trisomy 21

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Hilary HochbergGillian Lieberman, MD

In one large series of 1015 patients, nuchal translucency thickness of 3mm, 4mm, 5mm, and > 6mm increased risk of trisomy 3x, 18x, 28x and 36x higher than respective risk expected based upon maternal age alone.

Pandya PP, Kondylios A, Hilbert L, Snijders RJ, Nicolaides KH. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995 Jan;5(1):15-9.

**

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Hilary HochbergGillian Lieberman, MD

Nuchal Fold: 2nd Trimester• Thickened nuchal skin

fold Outer skull table to outer skin surface

• >6 mm abnormal at 19-24 weeks (83% specificity)*

• 40% Down’s fetuses have thickened fold

Benacerraf BR, Gelman R, Frigoletto FD: Sonographic identification of second-trimester fetuses with Down’s syndrome. NEJM 317:1371, 1987.

**

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Hilary HochbergGillian Lieberman, MD Choroid Plexus Cysts

•Present in 2% of normal pregnancies•Folding of neuroepithelium accumulate CSF•Most resolve by weeks 26-28.

http://www.thefetus.net/sections/articles/Technique/chapter-10/aneuploidies.html

Must be imaged in 2 orthogonal planes and > 3 mm.

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Hilary HochbergGillian Lieberman, MD

Echogenic Bowel

http://www.thefetus.net/sections/articles/Technique/chapter-10/aneuploidies.html

•0.5% normal fetuses•Usually no significance•Cause unknown

HypoperistalsisMeconium fluid content

Gut ischemia

Also found in cases of:• fetal viral infection, ex: CMV• small bowel atresia/volvulus• growth retardation• cystic fibrosis

•For isolated bowel changes, risk for trisomy 21 7x

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Hilary HochbergGillian Lieberman, MD

http://brighamrad.harvard.edu/Cases/bwh/images/35/Laing12US.GIF

Duodenal Atresia Double-bubble sign

•1/10,000 births•5-8% Down’s Syndrome fetuses•30% of fetuses with duodenal

atresia have Down’s Syndrome

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Hilary HochbergGillian Lieberman, MD

Echogenic Intracardiac

FocusImage 1 Image 2

•Single foci quadruples risk of Down’s syndrome

•3-8 % normal 2nd trimester ultrasounds

•Most commonly single foci in LV, can be multiple and bilateral

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Hilary HochbergGillian Lieberman, MD

Image1:http://www.thefetus.net/sections/articles/Technique/chapter-10/aneuploidies.htmlImage2: Winter, Thomas C, MD et al. Echogenic Intracardiac Focus in 2nd-Trimester Fetuses with Trisomy 21: Usefulness as a US Marker. Radiology 2000; 216; 450-456. Simpson J. Cardiac echogenic focus. 1999 Prenat Diagn 19:972-975.

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Hilary HochbergGillian Lieberman, MD

Atrioventricular Septal Defect•AKA endocardial cushion defect; 7% CHD; 1/3000 births

•Endocardial cushions form the lower atrial septum, the upper ventricular septum, the septal leaflet of the tricuspid valve and the anterior leaflet of the mitral valve. An ECD defect is due to abnormal development of these endocardial cushions.

•ASD+VSD a common opening to all chambers of heart

•>50% of DS fetuses have CHD (44% have AVSD) 43% of fetuses with AVSD have DS*

*Paladini D, Tartaglione A, Agangi A, Teodoro A, Forleo F, Borghese A, Martinelli P. The association between congenital heartdisease and Down syndrome in prenatal life. Ultrasound Obstet Gynecol 2000 Feb;15(2):104-8

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Hilary HochbergGillian Lieberman, MD

http://www.tmc.edu/thi/canal.html

http://www.acuson.com/cme/pdf/quiz30.pdf

AVSD

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Hilary HochbergGillian Lieberman, MD

Images: http://www.thefetus.net/sections/articles/Technique/chapter-10/aneuploidies.html

Short femur

Mild renal pelvic dilatation(>4 mm at <33 wks abnormal)

Sandal gap

Other sonographic features

Snijders RJM, Platt LD, Greene N, Carlson D, Krakow D, Gregory K, Bradley K. Femur length and trisomy 21: impact of gestational age on screening efficiency.Ultrasound Obstet Gynecol 2000; 16:142-145.

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Hilary HochbergGillian Lieberman, MD

Dilated Pelvis

Normal Pelvis

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Hilary HochbergGillian Lieberman, MD

Ultrasound screening for Down’s syndrome

Useful information

Confusion

Many trisomy 21 findings overlap with normal fetus findings

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Hilary HochbergGillian Lieberman, MD

Sonographic Index for DS: 2nd trimester fetus

FindingsMajor anomalyNuchal Fold >6mmShort FemurShort HumerusPyelectasis >4mmHyperechoic BowelEchogenic Focus

Score2211111

Callen, PW. Ultrasononography in Obstetrics and Gynecology. 4th edn. WB Saunders CO. Philadelphia 2000.

Score > 2 82% DS (4%false positive)

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Hilary HochbergGillian Lieberman, MD

Patient M.C.

Ultrasound: normal. Obstetrician offered amniocentesis because calculated risk of fetus with trisomy 21 > risk of amnio complications.

Patient expressed that she would not abort fetus regardless of amnio results; however, she and her husband wanted psychological preparation and requested karyotype analysis.

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Hilary HochbergGillian Lieberman, MD References

Bradley K. Femur length and trisomy 21: impact of gestational age on screening efficiency. Ultrasound Obstet Gynecol 2000; 16:142-145. Callen, PW. Ultrasononography in Obstetrics and Gynecology. 4th edn. WB Saunders CO. Philadelphia 2000.Devore, GR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2000; 16:133-141.Filly RA. Obstetrical sonography: the best way to terrify a pregnant woman. J Ultrasound Med 2000; 19: 1-5.Graupe M, Naylor C, Greene N, Carlson D, Platt L. Trisomy 21: Second-Trimester Ultrasound. Clinics in Perinatology 28 (2): 303-319.Paladini D, Tartaglione A, Agangi A, Teodoro A, Forleo F, Borghese A, Martinelli P. The association between congenital heart disease and Down syndrome in prenatal life. Ultrasound Obstet Gynecol 2000 Feb;15(2):104-8Pilu G, Nicolaides KH. Diagnosis of fetal abnormalities. The 18-23 week scan. The Parthenon Publishing Group: New York, 1999.Simpson J. Cardiac echogenic focus. 1999 Prenat Diagn 19:972-975.Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Second-trimester ultrasound to detect fetuses with Down syndrome: A meta-analysis. JAMA 285 (8): 1044-1055.Snijders RJM, Platt LD, Greene N, Carlson D, Krakow D, Gregory K, Sepkulveda W, Sebire NJ. Fetal echogenic bowel: a complex scenario. Ultrasound Obstet Gynecol 2000; 16: 510-514.Pandya PP, Kondylios A, Hilbert L, Snijders RJ, Nicolaides KH. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995 Jan;5(1):15-9.Twining P, McHugo J, Pilling D. Textbook of Fetal Abnormalities. Churchill Livingstone: London, 1999.

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Hilary HochbergGillian Lieberman, MD

Acknowledgments

• Dr. Gillian Lieberman

•Pamela Lepkowski

•Larry Barbaras & Cara Lyn D’amour