Prenatal Ultrasound Findings in Trisomy 21
by Beth A. Pletcher, MD, May 1999

Because second trimester ultrasound is often done as a part of routine prenatal care and potential risks of amniocentesis for many women outweigh the risks of having a child with a serious cytogenetic disorder, there has been great interest in the possible use of ultrasound to detect fetuses with Down syndrome as well as other common chromosomal disorders. Over the past decade many studies have explored the value of a variety of sonographic findings in detection of trisomy 21 with quite scattered results. In order to rationally evaluate these data, one needs to consider a number of variables including detection of anomalies versus non-specific "markers" as well as specificity and sensitivity of these sonographic findings. The question also arises as to whether the combination of maternal serum screening along with a sonogram can approach the detection rate using serum screening and amniocentesis for those patients identified to be at significant risk as determined by a reference lab.

Careful examination of the detection rate for trisomy 21 using major structural defects as the point of reference has been relatively poor and differs widely from study to study with detection rates between 7% and 50%. The vast majority of fetuses with Down syndrome will have a normal prenatal ultrasound primarily because routine studies are not very good at picking up cardiac anomalies which are by far the most common defects in children with this chromosomal disorder. On the other hand, clinicians are beginning to use a collection of ultrasound markers in practice to adjust a woman's risk of having a fetus with a trisomy in conjunction with maternal age and serum screening results. Because these so called markers are found in both normal and abnormal fetuses, it is only in the context of a specific pregnancy with possibly more than one marker or risk factor present that one can begin to examine the usefulness of these sonographic findings. The most common markers used for this type of prenatal evaluation include: choroid plexus cyst(s), nuchal fold thickening, intracardiac echogenic focus, renal pyelectasis, echogenic bowel, shorter than expected femur length, shorter than expected humerus length, shorter than expected ear length and camptodactyly (clenched fists). Some perinatologists also look for shorter than expected metacarpal length, increased space between the first and second toes as well as abnormal pelvic configuration (angle) to augment the sonographic picture.

The literature is full of studies examining these markers, but the small sample size, ascertainment bias and in some cases lack of outcome data have hampered clinicians in establishing which markers are adequately sensitive and specific. Most studies have looked simply at a single marker rather than combinations of markers and few have combined ultrasound data with maternal serum screening results. Just as maternal serum screening has become more sensitive with the addition of multiple biochemical markers, it is likely that only by combining screening for several ultrasound markers as well as maternal age and maternal serum results will the utility of ultrasound in the diagnosis of trisomy 21 and other aneuploidies be realized. Until such time as the correct identification of affected fetuses (sensitivity) approaches that of serum screening and maternal age, it is unlikely that ultrasound will replace amniocentesis as a diagnostic test. Over time it will also be important to evaluate the specificity of this screening methodology and closely examine multiple markers/factors in prenatal detection of Down syndrome and other cytogenetic abnormalities. In the meantime, clinicians will continue to use ultrasound as an adjunct to prenatal detection of cytogenetic abnormalities and in some settings be able to readjust fetal risks to aid couples in making more appropriate decisions regarding whether or not to proceed with amniocentesis.