None of the markers for Down syndrome on second-trimester ultrasonography are sensitive enough to reliably discriminate between affected and unaffected fetuses, a metaanalysis of 56 studies involving over 132,000 pregnancies has shown.
Physicians routinely counsel patients that the presence of one of these markers indicates an increased risk for Down syndrome and warrants amniocentesis for a definitive diagnosis. Not only do the data refute such risk estimates, they also suggest that this common clinical practice often does more harm than good, according to Dr. Rebecca Smith-Bindman of the University of California, San Francisco, and her associates.
"Clinicians should be very cautious about the use of these markers to counsel women about their risk of having a fetus with Down syndrome," they said (JAMA 285:1044-55, 2001).
Their metaanalysis included studies that measured the true-positive, false-positive, true-negative, and false-negative results for each of eight isolated ultra sound markers for Down syndrome: nuchal-fold thickening, choroid plexus cyst, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, shortened humerus, shortened femur, and fetal structural malformations.
Only one of these markers, a thickened nuchal fold, helped distinguish affected from unaffected fetuses. But a thickened nuchal fold is present in so few fetuses with Down syndrome that ultrasound screening for it remains impractical, the investigators said.
Because the sensitivity of these markers is so low and the occurrence of Down syndrome is so rare, more than 99% of fetuses with one of these markers will actually be unaffected.
When women undergo amniocentesis because one of these markers is found on ultrasound, "there will be inevitable losses of unaffected fetuses as a complication," Dr. Smith-Bindman and her associates said.
"If, for example, identification of an echogenic intracardiac focus is used as a basis for offering amniocentesis to pregnant women at low risk of carrying an affected fetus, two unaffected fetuses will be lost as a complication of amniocentesis for each correctly identified Down syndrome case," the researchers noted.
"Even for nuchal-fold thickening, more than 15,000 scans would need to be per formed in average-risk women and more than 6,000 scans in high-risk women to detect a single case of Down syndrome," they added.
Equally important is the possibility that high-risk women--such as older gravidas or those who have abnormal serum-testing results--may be dissuaded from having amniocentesis if their ultrasound studies show none of these markers. "This will reduce the prenatal detection of fetuses with Down syndrome," the investigators said.
The researchers emphasized that the metaanalysis conducted involved only ultrasound markers that are found in isolation. However, finding a combination of these markers may prove to be a more accurate measure of risk for a Down syndrome fetus.
COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group