Two new techniques, one using maternal blood and the other amniotic fluid, should give health-care providers new insight into the health of a baby before birth.

Unlike currently available prenatal genetic tests, the first test is non-invasive and uses maternal blood to detect some genetic disorders, such as thalassemia and cystic fibrosis.

The second test uses amniotic fluid collected during amniocentesis, but provides far more information on gene expression and fetal development compared with currently available tests.

Studies profiling both techniques appear in the Feb. 16 issue of the Journal of the American Medical Association.

“The genetic analysis of the fetus currently relies on invasive procedures, such as amniocentesis, which is associated with a risk to mother and unborn child,” said Sinuhe Hahn, co-author of the study focused on the maternal blood-based test, and director of the Laboratory for Prenatal Medicine at University Women’s Hospital in Basel, Switzerland.

“To overcome this risk, several alternative risk-free approaches are being examined, of which one of the most promising is the analysis of cell-free fetal DNA in maternal blood,” Hahn explained.

However, challenges remain when it comes to analyzing maternal blood. One major hurdle facing genetics experts is that it has been difficult to separate the mother’s DNA from the baby’s DNA in maternal blood, according to Hahn. Recently, however, researchers discovered that cell-free fetal DNA was smaller than maternal DNA, making it easier to separate the two. The process of separating maternal and fetal DNA molecules in blood is called size-fractionation.

To further ensure that they were looking at fetal DNA, the Swiss researchers turned to an advanced genetics technique that helps suppress maternal DNA.

Their ultimate goal was a method of separating out fetal DNA and then pinpointing specific mutations. To test whether they had achieved that goal, the researchers drew blood samples from 32 pregnant Italian women at risk for a genetic mutation for thalassemia, a type of anemia common in people of Mediterranean descent.

Using its newly developed technique, the Swiss team said it correctly identified the father’s defective gene in fetal DNA in between 81 percent and 100 percent of the cases.

The researchers hope to be able to expand the test’s capability to where it can identify cases where both the mother and the father have the same defect, Hahn said. The current test is only useful when the mother and father have different genetic mutations for thalassemia, she pointed out.

Hahn said the biggest advantages to this test are that it is both non-invasive and relatively cheap. The technique could also be useful for spotting serious conditions such as cystic fibrosis and Tay-Sachs syndrome in utero, according to Hahn.

In the second study, U.S. researchers report a new use for amniotic fluid that’s usually discarded after amniocentesis.

Typically, when amniocentesis is performed, cells are collected from the amniotic fluid and then fetal chromosomes are studied to look for problems such as Down’s syndrome, explained study co-author Dr. Diana Bianchi, vice chair of pediatric research at the Floating Hospital for Children and Tufts-New England Medical Center, Boston.

Once those cells are removed from the sampled amniotic fluid, the remaining fluid is generally discarded. But, Bianchi and her colleagues felt there might be valuable information still locked inside that fluid.

“What we found is that, in the amniotic fluid itself, [there] is vital information about the fetus,” she said.

By examining the fluid, the researchers were able to obtain information on thousands of genes and their patterns of expression. In the current study, the researchers focused on only those genes they thought would be developmentally important.

For example, salivary mucin is an important substance for the oral digestion of food, according to Bianchi. In the amniotic fluid of one 17-week-old fetus the investigators found no evidence of salivary mucin, which she said wasn’t surprising because the developing fetus has no need of orally digesting food. However, in fluid samples from fetuses near-term, the researchers did find salivary mucin, suggesting that as a baby nears birth a gene that tells the body to make salivary mucin gets switched on.

A more important finding was that in a set of twin fetuses, the gene that tells the body to make surfactant proteins, which are important for lung development, was turned on in one baby, but not in the other. The baby without surfactant proteins didn’t survive. Bianchi said one of the most potentially important uses for this test might be in women in preterm labor. It could give health-care providers a much more accurate way to assess the fetus’ developmental progress than is currently available.

“If you’re going to do an amniocentesis anyway, for the same risk, you can get much more info than is possible from the standard technique,” said Bianchi.

Both tests are in the preliminary stages and are not yet commercially available.

More information

To learn more about the types of prenatal tests that are currently available, go to the March of Dimes Web site (http://www.modimes.org ).