In the future it will be possible to screen pregnant women for serious genetic diseases in their unborn children.
A research team from Odense University Hospital and the University of Southern Denmark has developed an innovative screening test. With a blood sample from the expectant mother, they can analyze all the genes of the fetus.
In the results of a research project recently published in the New England Journal of Medicine, researchers analyzed blood samples from 36 pregnant women. The results show that the new test, called desNIPT, is effective in identifying changes in fetal genes that are an important factor in serious congenital diseases.
With our new method, we can now detect most of the known serious genetic syndromes using a simple blood test from a pregnant woman. Typically, this would require chorionic villus sampling or amniocentesis, says Ieva Miceikaité of the Department of Clinical Research at the University of Southern Denmark.
This means that we now have a better chance of identifying the genetic cause of developmental problems in fetuses.
First generation NIPT test
desNIPT represents an evolution of the first-generation NIPT (Non-Invasive Prenatal Test) procedure, adding significant improvements. NIPT involves testing without the need for chorionic villus sampling or amniocentesis, and is administered before the baby is born.
In this approach, fetal DNA found in a pregnant woman’s blood is examined, revolutionizing the ability to diagnose diseases in fetuses in recent years.
The DNA is released into the mother’s blood through the placenta. Thanks to the extraordinary sensitivity of the desNIPT test, researchers can now identify genetic abnormalities in fetuses even when the amount of fetal DNA in the mother’s blood is minimal.
Genetic disorders in the fetus can be identified by testing the mother’s blood.
Currently, first-generation non-invasive prenatal testing (NIPT) is used to screen fetuses for prevalent chromosomal disorders, focusing primarily on Down syndrome and some other conditions that are notable as a result of chromosomal changes.
However, many congenital diseases are caused by more subtle changes in fetal DNA. To identify them, it is necessary to examine all the genes in the embryo’s genome, explains Ieva Miceikaité.
This test, called exome sequencing, is currently limited to pregnancies in which signs of abnormalities are seen during an ultrasound. This restriction is because the test currently requires chorionic villus sampling or amniocentesis, both procedures associated with discomfort and a slight risk of miscarriage. As a result, many serious genetic syndromes are often not detected until after birth.
Our goal was to expand non-invasive screening options for pregnant women. The new desNIPT test combines the advantages of NIPT and exome sequencing, providing complete information through a simpler test, explains Ieva Miceikaité.
Get similar results with a simpler test
Together with her research colleagues, Ieva Miceikaité followed 36 pregnant women, analyzing blood samples taken during the first or second trimester. In each pregnancy, ultrasounds identified a potentially serious genetic disease in the fetus.
Of the 36 pregnancies, disease-induced changes in the newborn were identified in a total of 11 cases. The results of desNIPT analysis were then compared with the results of conventional exome sequencing performed by chorionic villus sampling or amniocentesis.
The new method of detecting pregnant women has had notable success, says Ieva Miceikaite and adds:
By applying the new analytical method, we successfully identified all genetic variants responsible for diseases previously detected by invasive fetal examinations. In this sense, it has demonstrated effectiveness against these invasive procedures.
A promising future for prenatal screening
The test opens up the possibility of detecting many more genetic diseases in the future, including those that cannot be detected by ultrasound, explains Martin Larsen, project leader and Department of Clinical Research at the University of Southern Denmark and associate professor.
He envisions significant potential in implementing the test as a screening tool alongside ultrasound examinations (the predominant standard for all pregnant women) to ensure more thorough prenatal screening of expectant mothers.
A notable challenge with multiple screening tests is their inconsistent accuracy, often resulting in unnecessary follow-up diagnostic testing.
We are extremely optimistic because the study indicates that the desNIPT test is remarkably accurate. “In the pregnant women analyzed we did not find any false positives,” says Martin Larsson.
Because this is a “proof of concept” study, the test needs validation in larger studies before it can be available to pregnant women.
Initially, our goal was to establish the feasibility of sequencing fetal genes using a blood sample from a pregnant woman. Currently, our goal is to validate the test through a larger study, as well as to refine and expand the method, says Martin Larsson.
