Here's the scenario. A soon-to-be mom wants to make sure her unborn child is born healthy into the world. She wants to have prenatal testing done, but there is a chance such a method could cause her to miscarry. So does she risk the health of her baby undergoing the genetic testing that could ultimately help the child in the long run?
Thanks in part to a group of scientists and researchers at Stanford University (Stanford, California), the Howard Hughes Medical Institute (Chevy Chase, Maryland) and Lucile Packard Children's Hospital (Palo Alto, California), the expecting mom won't have to make such a difficult choice. The group has created a test, which requires only a maternal blood sample to spot chromosomal disorders such as Down syndrome.
"Developing this test has been a decades-long race," Steven Quake, PhD, a professor of bioengineering and the study's senior author, told Medical Device Daily. "Response to our findings has been overwhelming.
The new technique, which takes advantage of fragments of fetal DNA in the woman's blood, will be published online this week in the Proceedings of the National Academy of Sciences.
It differs from traditional methods of testing such as amniocentesis and chorionic villus sampling, which require inserting a needle in the uterus and carry a miscarriage risk of around half a percent.
The probes often are inserted into the placenta, e.g., amniocentesis, which can be done from about 14 weeks' gestation, and usually up to about 20 weeks and chorionic villus sampling, which can be done earlier (between 9.5 and 12.5 weeks gestation), but which is slightly more risky to the unborn child.
"Non-invasive testing will be much safer than current approaches," Quake said.
According to Quake, the new method scans for fetal aneuploidy, an abnormality in the number of fetal chromosomes. Humans typically inherit 46 chromosomes, half from each parent. When there is an error in the chromosome numbers then serious defects can occur. Down syndrome, for example, arises from an extra copy of chromosome 21.
The team developed a way to count chromosomes using bits of fetal DNA in a pregnant woman's blood. This had been problematic for scientists over the years as they had struggled to tease these tiny genetic clues apart from a mom's DNA, Quake said. His team came up with a simple solution in that their new method has no need to distinguish between maternal and fetal DNA.
First, using samples from 12 women with aneuploid pregnancies and six with normal pregnancies, the researchers separated maternal blood into cells and plasma. They discarded the blood cells, focusing on the liquid plasma's DNA fragments, which come from both the mom and the fetus. They counted the number of DNA fragments and used DNA sequencing to read each one.
"You randomly sequence whatever is there," explained Christina Fan, a doctoral student in bioengineering who was the study's lead author. The DNA fragments are 25 to 30 base pairs long, she said, long enough to match each fragment to a specific chromosome.
The researchers tallied how many gene fragments originated from each chromosome. Women with Down syndrome pregnancies had more chromosome-21 fragments in their blood than women with normal pregnancies. Other forms of aneuploidy could be detected, too.
Because fetal DNA shows up in maternal blood quite early in pregnancy, the team says their technique could provide a much earlier diagnosis for fetal aneuploidy than is now available.
"The earlier you know you've got a fetus with Down syndrome, the better able you are to prepare," Quake said, noting that the benefit holds both for women who keep and those who terminate such pregnancies.
He added that the group was "looking to do the test at about five weeks into pregnancy." "When we look at our sensitivity, we'll be able to do this test as early as the fifth week of pregnancy. In our study, our earliest times testing a patient was in the 10th week and the 14th week. We think we can do quite a bit better."
Quake said the group wanted to look at a larger number of women for a new study. He said he expects it will take the new test two to three years to reach the clinic, assuming that the larger trial is successful.
The next step is only the tip of the iceberg and has Stanford filing a patent application for the new technique, and Quake consults for two potential licensees.
"This technique is on the leading edge of a flood of different ways that rapid DNA sequencing will be used in medicine," he said.