Diagnostic Imaging
January 2003

OVERREAD

Ultrasound finds new Down syndrome marker

Researchers are breaking ground with new noninvasive procedures to more accurately diagnose genetic anomalies during pregnancy's early stages. In a recent study, Argentinean researchers found that the absence of nasal bone in a first trimester ultrasound exam indicates that the fetus will almost certainly develop Down syndrome.

The investigative team from the Italian Hospital in Buenos Aires confirmed the absence of nasal bone in three of five fetuses later found to have Down syndrome. The study assessed 194 consecutive fetuses from singleton pregnancies with transabdominal ultrasound prior to chorionic villi sampling screening for aneuploidy. The findings published in the October issue of Prenatal Diagnosis confirmed the results of previous British studies.

A full view of the fetal profile had a success rate of 94%, meaning it was not always possible for sonographers to confirm the absence or presence of nasal bone. Absence of nasal bone is not related to nuchal translucency thickness, however, and using both markers along with maternal age could provide an effective method of early screening for trisomy 21, increasing sensitivity and reducing false-positive rates (Cicero et al. The Lancet 2001;358:1665-1667).

The most significant finding is that normal fetuses almost always have visible nasal bones, said Dr. Lucas Otano, ob/gyn service chief at the Italian Hospital. The false-positive rate his study recorded was less than 1%.

The nasal bone observation is a powerful noninvasive test for detecting Down syndrome in the late first trimester, according to Dr. Beryl Benacerraf, a clinical professor of radiology and ob/gyn at Harvard Medical School.

"While amnio is the only definitive test to detect chromosomally abnormal fetuses, the nasal bone appearance by ultrasound will identify fetuses at increased risk," she said.

A study that was published in the December issue of the Journal of Ultrasound in Medicine, authored by Dr. Bryann Bromley and coauthored by Benacerraf, discusses the use of the nasal bone measurement in second trimester rather than first trimester fetuses.

"Many patients don't have ultrasound until the second trimester," Benacerraf said. "The nasal bone marker can still be used successfully to detect fetuses at risk for Down syndrome at the time when most women undergo their ultrasound for structural survey."

Large prospective studies of low-risk populations are still needed to establish the reproducibility of the ultrasound technique and to evaluate the potential use of the nasal bone examination with other known markers, Otano said. Similar studies suggest the predictive power of physiological markers may vary depending on the race of the parents, for example.

The findings may reduce the need for invasive diagnostic procedures, such as chorionic villi sampling, to screen for chromosomal anomalies, according to Otano.

"The high specificity might prevent a significant proportion of invasive procedures in the screened population," he said.

Combining ultrasound and various biochemical tests to screen for trisomy 21 has helped to increase the overall accuracy substantially. Researchers have achieved detection rates of 91.6% during the first trimester using a combination of ultrasound with assessments of free b human chorionic gonadotropin, serum a-fetoprotein, unconjugated estriol (uE3), pregnancy-associated plasma protein-A, and nuchal translucency.