Ultrasound Markers for Down Syndrome
Down Syndrome (trisomy 21) is the most common chromosomal disorder in live born infants. About 6,000 babies are born with Down Syndrome each year in the United States, or about 1 in every 700 births. There are multiple prenatal genetic screening strategies and diagnostic tests aimed at accurate prenatal identification of Down Syndrome and other aneuploidies.
Ultrasound is a key component of aneuploidy screening. Both major structural abnormalities and minor “soft markers” can be detected by ultrasound in fetuses affected with aneuploidies. Down Syndrome can include cardiovascular, central nervous, craniofacial, musculoskeletal, gastrointestinal, and urinary tract system anomalies. Major structural anomalies include duodenal atresia and cardiac anomalies such as septal defects, tetralogy of Fallot, and atrioventricular canal defects. These anomalies are not always detected by prenatal ultrasound screening.
Nuchal translucency (NT) can be assessed in the first trimester. NT reflects the subcutaneous fluid-filled space between the back of the fetal neck and the overlying skin. There is an association between increased NT measurement and risk of aneuploidies, including Down Syndrome, with the detection rate for Down Syndrome being 64-70%. A nuchal cystic hygroma represents pathologic nuchal edema and is associated with aneuploidy, including Down Syndrome, in about 50% of cases. A hypoplastic or absent nasal bone can be detected in the first trimester in 62-70% of fetuses with Down Syndrome, but is present in only 1% of normal fetuses.
In the second trimester, the most commonly assessed soft markers include echogenic intracardiac foci, pyelectasis, short femur length, choroid plexus cysts, echogenic bowel, thickened nuchal skin fold, and ventriculomegaly. While the likelihood ratios associated with the first four are generally less than 2, the likelihood ratios for echogenic bowel, thickened nuchal fold, and ventriculomegaly are all over 5. The predictive value for echogenic bowel, thickened nuchal fold, and ventriculomegaly, even when isolated, is sufficiently high to prompt further genetic counseling and offering additional aneuploidy screening or diagnostic testing. Findings with lower predictive values such as an isolated choroid plexus cyst, echogenic intracardiac focus, or pyelectasis may prompt aneuploidy screening if not already done. The probability of Down Syndrome is increased when multiple soft markers are present and may prompt diagnostic testing. As an isolated finding, an increased nuchal skin fold confers the highest risk of aneuploidy and is the most powerful second trimester ultrasound marker, with a likelihood ratio of 11-18 and > 99% specificity for Down Syndrome.
Ultrasonography should not be used by itself to diagnose or exclude Down Syndrome. Sensitivity for detecting Down Syndrome is increased when ultrasound findings are interpreted in combination with serum analyte screening tests such as first and second trimester screening and integrated and sequential screening. Cell-free DNA has a detection rate for Down Syndrome of 99%. Diagnostic testing, such as amniocentesis or chorionic villus sampling, should be offered when screening test results are positive.
American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020 Oct;136(4):e48-e69. doi: 10.1097/AOG.0000000000004084. PMID: 32804883.
Committee on Practice Bulletins—Obstetrics and the American Institute of Ultrasound in Medicine. Practice Bulletin No. 175: Ultrasound in Pregnancy. Obstet Gynecol. 2016 Dec;128(6):e241-e256.
Initial approval: November 2017. Reaffirmed May 2019, Reaffirmed January 2021, Minor Revision July 2022
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