Yale to Begin Clinical Trial for New Test to Provide Earlier Detection of Down Syndrome

A new screening test that could significantly improve the detection of fetal Down syndrome will be tested in a national clinical trial by Yale researchers beginning in January.

The modified urine pregnancy test, hyperglycosylated hCG (HhCG), was developed at Yale. The principal investigators in the trial will be Maurice Mahoney, M.D., and Ray Bahado-Singh, M.D., both of the Yale School of Medicine.

The most commonly used test is the triple screen blood test, which is administered in the second trimester and has an accuracy rate of about 60 percent. Earlier studies conducted at Yale using urine HhCG suggest an accuracy rate of 80 percent in the second trimester.

A screening test tells the patient the probability that a medical condition exists. A diagnostic test tells the patient whether the condition exists.

Mahoney and Bahado-Singh said improved accuracy of Down syndrome screening would mean fewer women would undergo amniocentesis to obtain a definitive diagnosis.

Amniocentesis is a procedure in which a small sample of amniotic fluid is drawn out of the uterus through a needle inserted in the abdomen. The fluid is then analyzed to detect genetic abnormalities in the fetus. There is a minimal risk to the fetus.

“To have a test that performs better, that means fewer amniocenteses and a higher percentage of abnormal babies identified, is a very good outcome for the public and for parents,” said Mahoney, professor of genetics, obstetrics and gynecology, and pediatrics. “It is both of these concerns that drive the desire to have a better screening test.”

Down syndrome is a congenital disorder caused by the presence of an extra 21st chromosome. The affected person has mild to moderate mental retardation, short stature, and a flattened facial profile. Pregnant women age 35 or older are statistically at higher risk of giving birth to a child with Down syndrome.

The clinical trial of the new test is expected to last six months. More than 10,000 pregnant women, half in the first trimester (11-13 weeks) and half in the second trimester (14-20 weeks), will be enrolled. Each patient will be given a series of Down syndrome screening tests – ultrasound, urine and blood test – to compare their accuracy.

The new urine test was developed by Lawrence Cole, a biochemist, and the patent, jointly owned by Yale and Cole, has been leased to Quest Diagnostics. The clinical trials will be conducted in California, Philadelphia, North Carolina, Seattle and Massachusetts, as well as in the New Haven area.

Bahado-Singh, associate professor in the Department of Obstetrics and Gynecology, said sensitive, early detection of Down syndrome and other chromosomal defects would, most importantly, reduce anxiety for the prospective parents. If HhCG proves to be highly sensitive in the first trimester, he said, it also would reduce the frequency and the medical risk of terminating a second, rather than a first, trimester pregnancy.

He said the traditional triple screen blood test misses about 40 percent of fetal Down syndrome cases in the mid-trimester and is not sufficiently effective in predicting who might test positively in an amniocentesis test.

“Between 60 to 100 amniocenteses now are performed to identify each case of Down syndrome,” Bahado-Singh said. “There is a small but significant risk of miscarriage related to the amniocentesis itself (about one in 200).”

Lowering health care costs also is a factor, he said, since each amniocentesis test costs $1,500 to $2,500.

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