New method allows noninvasive prenatal testing to detect more diseases: study

Researchers from the United States and China said Monday they have developed a method to expand the types of chromosomal abnormalities that a simple blood test called noninvasive prenatal testing (NIPT) can detect.

The study, published in the U.S. journal Proceedings of the National Academy of Sciences, used a semiconductor sequencing platform to identify small chromosomal deletions or duplications, such as those occurring in Cri du Chat Syndrome and DiGeorge Syndrome, with blood plasma from the expectant mother.

Detecting these types of small chromosomal abnormalities with conventional techniques usually requires an invasive procedure to obtain fetal DNA, such as amniocentesis or chorionic villus sampling, which carries a small but concerning risk for miscarriage and infection.

Since the recent discovery that fetal DNA can be found in the blood of pregnant women, the NIPT has been increasingly used to detect certain chromosomal abnormalities through a maternal blood test.

So far, the NIPT is typically used only to detect abnormalities that result from larger chromosomal abnormalities -- too many or too few of a particular chromosome, for example, such as occurs in Down syndrome.

"We have found that NIPT can be extended in a way that allows us to zoom in and examine a small segment of a chromosome," lead author Kang Zhang, professor at the University of California, San Diego, said in a statement.

"And while this study focused on cell-free DNA sequencing in pregnant women, this method could be applied more broadly to other genetic diagnoses, such as analyzing circulating tumor DNA for detection of cancer," he said.

Zhang and his team analyzed blood plasma from 1,476 pregnant women with fetal structural abnormalities detected by ultrasound. These women also underwent an invasive diagnostic procedure and conventional fetal DNA analysis.

The researchers compared that information to semiconductor sequencing results on circulating fetal DNA obtained from a blood test on the pregnant women at an average gestational age of 24 weeks.

The new semiconductor sequencing method detected 69 of 73, or 94.5 percent of abnormalities that are larger than one million base pairs.

The cost of semiconductor sequencing is less expensive than that of the conventional method, the researchers said, and it avoids an invasive procedure.

While promising, there is still room for improvement before semiconductor sequencing can be used routinely with the NIPT.

In the study, semiconductor sequencing detected 55 false positives, of which 35 were due to maternal, rather than fetal, chromosomal abnormalities. That means the new method will require a validation test to screen out maternal abnormalities.

The NIPT with semiconductor sequencing also needs to be tested at early time points in the pregnancy -- at 12 to 16 weeks, the researchers said.

The study, funded in part by the National Science Foundation of China, also involved researchers from Guangdong Women and Children Hospital, Guangdong Thalassemia Diagnostic Center, West China Hospital and Sichuan University. Endit