Summer 2005

New First-Trimester Screening for Down Syndrome

First-trimester detection of begins at home for many women coming to UCSF Benioff Children's Hospital. They start by pricking their fingers at home and spotting a piece of filter paper, which they send to a referral laboratory under a program pioneered at UCSF Benioff Children's Hospital. By the time the women come to the clinic at UCSF for the ultrasound portion of this "combined test," the blood will already have been analyzed to detect levels of key fetal proteins. That blood analysis, combined with high-resolution measurements of the nuchal translucency, can detect 90 percent of Down syndrome cases in fetuses 11 to 14 weeks old.

Old Test More Invasive

For years, testing for Down syndrome was only offered to women age 35 and older. Amniocentesis in the second trimester was, for decades, the only available test for Down syndrome. More recently, chorionic villi sampling (CVS) offered screening for genetic abnormalities in the first trimester. Both methods, however, require the insertion of a needle or catheter directly into the uterus, a process that women often find frightening or uncomfortable, and that carries a risk of miscarriage.

Maternal blood analysis in the second trimester has also been used as a screening tool, but this method detects only 60 percent of Down syndrome cases, and provides a high number of false positive results. In addition, the later gestational age and late reporting of results discourage women from using this test.

In the late 1990s, UCSF Benioff Children's Hospital became one of the first in the country to offer nuchal translucency (NT) assessment after it was demonstrated that an enlarged NT is associated with fetal Down syndrome. On its own, NT measurement provides a 75 percent detection rate for Down syndrome.

Newer Approaches

More recently, UCSF clinicians began offering combined NT ultrasound screening with newer blood tests in the first trimester, an approach that had been reported to be more effective in a large study published in the New England Journal of Medicine. The older "triple screen," or "expanded AFP," measures levels of three key molecules: alpha fetoprotein, human chorionic gonadotropin (hCG) and estradiol. Clinical researchers had discovered, however, that more accurate and earlier screening was possible by measuring levels of the free beta subunit of hCG and of PAPP-A (pregnancy-associated plasma protein A).

A very large trial, dubbed FASTER (First and Second Trimester Evaluation of Risk), has been conducted in the US to compare the various screening methods for Down syndrome. The results have been presented at various conferences and are expected to be published soon.

UCSF was the first site to introduce the concept of blood testing at home prior to the NT ultrasound, which provides several advantages. The major advantage is that clinicians are able to obtain the results of the test immediately after the ultrasound. Mary Norton, M.D., director of perinatal medicine and genetics in the Obstetrics, Gynecology and Reproductive Sciences department, reports that women are glad to get their results quickly.

"Patients are happy to get their results the same day," Norton says. "And if the results indicate an increased risk, it gives us the chance to counsel the patient and let her understand her options." Many patients with an abnormal test result are able to have definitive testing with CVS the same day, substantially decreasing the period of waiting and anxiety. Another benefit of earlier blood testing is that the test is actually somewhat more sensitive at an earlier gestational age, while the NT ultrasound performs better at a somewhat later gestational age. Timing the blood and ultrasound optimizes test performance while providing patients with the convenience and reassurance of receiving all of their results at one time.

For more information, contact Dr. Norton at (415) 476-4157.

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