By Diagnostics World Staff
August 7, 2018 | Diana Bianchi argues that sequencing fetal DNA could reduce the need for invasive prenatal diagnostics. Bianchi and Rossa Chiu outline their case in a review article published earlier this month in the New England Journal of Medicine (DOI: 10.1056/NEJMra1705345).
Fetal DNA circulates in a pregnant woman's blood, and it’s been the target of many non-invasive tests. Bianchi and Chiu call the sequencing of this DNA “a success story of modern genomic medicine.”
Bianchi is an expert in the field. Before her current post as senior researcher and institute director at the National Institutes of Health, Bianchi was Executive Director of the Mother Infant Research Institute at Tufts Medical Center, a Professor of Pediatrics and Obstetrics and Gynecology at Tufts University School of Medicine in Boston, and chair of the clinical advisory board at Verinata Health (which was
acquired by Illumina in 2013).
In the NEJM review article, Bianchi and Chiu explained that fetal DNA sequencing improves the accuracy of prenatal screening tests for genetic conditions and at times has led to the diagnosis of maternal conditions that may have otherwise gone undetected.
The blood test analyzes fetal DNA that enters a pregnant woman's blood from her placental cells. It most commonly is used to screen for Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome). It also has been used to detect conditions resulting from an extra sex chromosome, from a missing part of a chromosome, and even for conditions resulting from a single gene mutation. “Some [professional] guidelines also support cfDNA testing for all women, because it is the most sensitive test for these common autosomal aneuploidies,” the authors note.
But there are drawbacks to this type of testing. cfDNA testing is more expensive than other tests, though some insurers in the U.S. cover this type of testing for high-risk mothers. In addition, “the resources and efforts that are required for pretest counseling associated with maternal plasma cfDNA testing are greater than those re- quired for counseling associated with the standard screen,” Bianchi and Chiu say.
The counseling issues can be complicated. The American College of Medical Genetics and The American College of Obstetricians and Gynecologists caution that patients and their clinicians should know that fetal DNA sequencing is a screening test and not a diagnostic test. Among women who test negative for any abnormalities, cell-free DNA sequencing may reduce the need for additional prenatal testing procedures, some of which may increase miscarriage risk. Confirmatory testing should continue to be offered to women with positive results.
“In consenting to a blood test that poses no fetal risk, some women may not be fully aware of the limitations of the test or they may give inadequate consideration to the effect of potentially receiving a positive result,” the authors say.
There could also be counseling issues for the mother as well. Because maternal DNA is also in the blood sample, it is sequenced along with fetal DNA, which may lead to incidental findings, or detection of conditions in the pregnant woman, including blood abnormalities and sex chromosome abnormalities.
On the whole, however, Bianchi and Chiu are positive about the development of cfDNA research space and its implications for clinical care. “The clinical adoption of cfDNA sequencing for chromosomal aneuploidy screening has already had a global effect,” they write. “Maternal plasma cfDNA sequencing represents a major advance in genomic medicine that has resulted in more precise screening, reduced invasive procedures, and created multiple ethical challenges.”
Editor's Note: Cambridge Healthtech Institute will host the 6th Annual Advances in Prenatal Molecular Diagnostics event in October. Sessions will be dedicated to non-invasive prenatal testing, cell-free DNA screening, and more.