Test Boosts Fetal DNA in Mom's Blood

Advance could lead to less invasive tests for expectant mothers

TUESDAY, March 2, 2004 (HealthDayNews) -- A simple change in the way maternal blood is treated increases the amount of fetal DNA in the blood, which could eventually lead to less invasive prenatal testing for genetic defects.

By adding the preservative chemical formaldehyde to blood samples from expectant mothers, researchers were able to raise the average amount of available fetal DNA from about 8 percent to more than 20 percent.

Results of the study appear in the March 3 issue of the Journal of the American Medical Association.

Currently, the most reliable ways to test for prenatal genetic defects are tests called amniocentesis and chorionic villus sampling. While these tests are very accurate, they are invasive and carry a small risk of miscarriage.

"The main purpose of doing this study was to try to develop a means of noninvasive maternal testing. One of the steps is to find ways to get fetal DNA out of the mother's blood," says study author Dr. Ravinder Dhallan, chief executive officer and founder of Ravgen Inc. in Columbia, Md.

Normally, the percentage of fetal DNA found in a mother's blood sample is very low, "about 3 percent in maternal blood samples," Dhallan explains.

Dhallan and his colleagues thought the actual percentage was higher, and theorized that if they added formaldehyde to mothers' blood samples it would "harden" or preserve the fetal DNA.

In the first phase of the study, the researchers tested two blood samples each from 10 pregnant women recruited from a single U.S. site. One of the samples from each woman was treated with formaldehyde; the other was not.

The percentage of DNA found in the untreated blood samples was 7.7 percent, while the formaldehyde treated samples averaged 20.2 percent fetal DNA.

During the second phase of the study, the researchers gathered 69 maternal blood samples from 27 different sites in 16 U.S. states. All were treated with formaldehyde.

About 59 percent of these samples had more than 25 percent fetal DNA. Just over 27 percent had more than 50 percent fetal DNA.

Dhallan says he believes formaldehyde stops the mother's blood cells from destroying themselves and overwhelming the fetal DNA. He says normally when blood is collected and transported, some of the blood cells burst and release their DNA into the mother's plasma. This reduces the percentage of fetal DNA.

He says this technique is something that could be easily duplicated in other labs, and says these findings have made it "more likely that in the future there will be a test from blood that can give you the same information from amniocentesis and other invasive tests."

In an editorial in the same issue of the journal, Dr. Joe Leigh Simpson, chairman of obstetrics and gynecology at Baylor College of Medicine in Houston, says the implications of this test are far-reaching.

"The real excitement is how we can use this in other ways," he says.

Not only could testing of fetal DNA look for genetic abnormalities, but it can detect earlier in pregnancy if a mother with Rh negative blood is carrying an Rh positive baby, which means all Rh negative women wouldn't need to receive preventive shots at 27 weeks' gestation to avoid developing potentially harmful antibodies.

Simpson also believes that in the future it may be possible to use fetal DNA to predict whether a pregnancy will have complications.

He also says the methods used to capture cell-free fetal DNA could be used to test for cell-free cancer DNA, which could be a better surveillance method than imaging technology for people diagnosed with cancer.

"This could be used as an early warning," says Simpson. "Molecular testing is far more sensitive than imaging."

More information

To learn more about amniocentesis and chorionic villus sampling, go to the March of Dimes or the American Academy of Family Physicians.

SOURCES: Ravinder Dhallan, M.D., Ph.D., chief executive officer and founder, Ravgen Inc., Columbia, Md.; Joe Leigh Simpson, M.D., chairman, Department of Obstetrics and Gynecology, and professor, Departments of Obstetrics & Gynecology and Molecular and Human Genetics, Baylor College of Medicine, Houston; March 3, 2004, Journal of the American Medical Association
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