Rapid advancements in genetic testing have hit the prenatal world, prompting a number of changes already and promising additional developments in the coming years.
Even as the number of women undergoing amniocentesis or chorionic villus sampling (CVS) has declined, the emergence of chromosomal microarray to replace karyotyping has yielded a chromosomal windfall of sorts with many more details coming from a single screening test. What to do with the information, and which patients benefit from having a test that not all insurance companies cover, creates a combination of logistical and clinical decisions for patients and providers to navigate.
On the screening side, improved accuracy and the ability to check risk factors for an increasing number of genetic disorders has also posed challenges with affordability and which patients would benefit.
Keeping pace can be a dizzying experience for a fetal-medicine specialist, let alone for a general obstetrician who is responsible for the overall care of their pregnant patients.
“The provider is in a tough situation, and understanding all of this is really complicated,” said Mary Norton, MD, University of California, San Francisco, Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences. That the professional organizations are still sorting out the best standard practices as they seek to keep pace with the latest advancements and the wait for well-designed scientific studies, only magnifies the situation, she said.
When it comes to screening, there are three main tips experts want clinicians to keep in mind:
1. Remember the importance of traditional serum marker testing
Often lost in the conversation over the next best genetic test is the importance and reliability of the traditional serum marker blood screenings that have served patients and physicians well for years, said Norton, who is also a past board member of the Society for Maternal-Fetal Medicine.
While much of the focus has revolved around the accuracy of detecting Down syndrome, the fear has been that if new cell-free DNA screenings replace the traditional tests, some useful information for the care of mother and baby will be lost, Norton said. Besides giving a risk factor for Down syndrome, the traditional test can detect other obstetrical complications, such as preeclampsia and risk of premature delivery.
"Those two are much larger contributors to poor pregnancy outcomes than Down syndrome,” Norton said. “While we don’t have great ways to prevent them, knowing the risk can provide information that providers have come to rely on in figuring out who is at high risk.”
2. Understand the NIPT evolution
While advancements in NIPT using fetal DNA from the mother’s blood can detect nearly all cases of Down syndrome – returning false-positive results in fewer than 1% of cases – there are slight differences in how each of the four laboratories conduct the tests, said Jennifer Hoskovec, president of the National Society of Genetic Counselors.
“It is very important if an OB is doing the screenings in their office to understand what each lab offers in comparisons to others,” she said.
Plus, she said the labs are regularly changing their screenings, coming out with slightly newer versions. The nuances are important to evaluate for our understanding of the science behind the screenings and ensuring that the evidence is supported by peer-reviewed research.
“It is very much a moving target because the technology is moving so rapidly,” she said.
In addition, NIPT is expensive and, while it may be a good secondary screening test for those at high risk for Down syndrome, more research and development needs to happen to improve the gene sequencing provided in the results, Norton said.
3. Blood tests are not diagnostic tests
Even with improved accuracy, NIPT and traditional blood tests are not on the verge of replacing diagnostic testing. CVS or amniocentesis are the only means to diagnose a chromosomal disorder. The message, while obvious to many, is one that has been lost in the hype surrounding the improvements to noninvasive testing, said Michelle Strecker, director of genetic counseling services for CombiMatrix one of the clinical diagnostic laboratories specializing in cytogenomic diagnostic testing.
Microarray results have proved screenings incorrect, she said. “It is not melodramatic to say that several times we have prevented terminations of babies who end up being healthy. Basically you save a life.”