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Study reports improved method to identify fetal DNA in maternal blood samples


A new method to increase the recovery of DNA from unborn babies in a blood sample from their mothers may be helpful for future development of non-invasive prenatal genetic tests to identify fetal abnormalities, according to an article in the March 3 issue of The Journal of the American Medical Association (JAMA).

"Prenatal diagnosis is useful in managing a pregnancy with an identified fetal abnormality and may allow for planning and coordinating care during delivery and the neonatal period," the authors provide as background information. "... invasive diagnostic tests (e.g., amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling) for fetal chromosomal abnormalities are highly reliable, but the procedure used for each test carries a risk for loss of pregnancy. Many patients who are candidates for these tests decline them because of the risk of pregnancy loss." The authors continue, "... the use of free fetal DNA for detecting chromosomal abnormalities has been limited by the seemingly low percentage of free fetal DNA in the maternal circulation."

Ravinder Dhallan, M.D., Ph.D., from Ravgen, Inc., Columbia, Md., and colleagues, analyzed blood samples from pregnant women to determine if the percentage of free fetal DNA could be increased by using formaldehyde to stabilize blood cell membranes and reduce the number of the mother’s blood cells that are destroyed during sample collection, handling, and processing, which reduces the amount of maternal DNA released, thereby increasing the percentage of fetal DNA. The study was conducted in two phases from January through February 2002 at one clinical site and March 2002 through May 2003 at a network of 27 clinical sites in 16 U.S. states. The first phase collected two samples of blood from ten pregnant women - one blood sample was treated with formaldehyde and the other blood sample was untreated. In the second phase, all 69 blood samples were treated with formaldehyde.

"In the first phase of the study, the mean (average) percentage of free fetal DNA in the untreated samples was 7.7 percent, while the mean percentage of free fetal DNA in the formaldehyde-treated samples was 20.2. percent. In the second phase, a median (half-way point) of 25 percent free fetal DNA was obtained for the 69 formaldehyde-treated maternal blood samples. Approximately 59 percent of the samples in this study had 25 percent or greater fetal DNA, and only 16 percent of the samples had less than 10 percent fetal DNA. In addition, 27.5 percent of the samples in this study had 50 percent or greater fetal DNA."

The authors conclude, "When samples have a high percentage of free fetal DNA, the difference between the expected ratio of the chromosomes for a healthy fetus and that for an abnormal fetus is greater, which makes it easier to diagnose chromosomal abnormalities," and suggest that their methods "for increasing the percentage of free fetal DNA provide a solid foundation for the development of a noninvasive prenatal diagnostic test."

Susan Higgins | EurekAlert!
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