Prenatal Genetic Testing Is Rapidly Evolving. Here’s Why That Matters.

When most people think of DNA testing, they imagine dramatic courtroom scenes from TV shows in which a crime’s perpetrator is revealed. We also now regularly hear stories of people using DNA tests to answer questions about their ancestry, sometimes discovering blood relatives they didn’t know they had.

In the context of pregnancy, the role of DNA testing is to uncover genetic disease in a foetus. (An additional bonus for parents is learning the baby’s sex, which many are eager to know.) Unfortunately, genetic testing in pregnancy often isn’t as conclusive or uncomplicated as the DNA testing police use to determine whether someone was at the scene of a crime. 

A recent study shows that more extensive testing can be done via a maternal blood test earlier in pregnancy than the tests we currently have access to. This means that expectant parents will soon be able to know a lot more about their baby’s genome early on, potentially identifying many genetic diseases during the first trimester of pregnancy. 

However, the results of these tests aren’t always clear-cut, and patients may need help understanding what they mean and whether to pursue additional testing. 

What kind of prenatal genetic testing is available now?

Currently in the U.S., pregnant patients are offered two types of testing: screening tests and diagnostic tests. Screening tests are generally offered toward the end of the first trimester. One screening test is the cell-free foetal DNA test (sometimes called non-invasive prenatal testing, or NIPT), which requires only a blood sample from the pregnant person. Another is the nuchal translucency exam, which measures a fluid-filled space on the back of the foetus’ neck, performed via ultrasound. These tests are used to screen for several chromosomal abnormalities, including Down syndrome, or trisomy 21.

Because both of these tests are considered screening tests, they will indicate the odds that your baby has a condition — not a diagnosis. Depending on the results of those tests, you may be offered a diagnostic test to determine if the foetus indeed has a genetic condition. These tests, chorionic villus sampling (CVS) and amniocentesis, are offered a little later in pregnancy: CVS at 11 to 13 weeks and amniocentesis at 15 to 20 weeks. These tests examine samples of DNA taken from either the placenta (CVS) or the amniotic fluid surrounding the foetus (amniocentesis). Diagnostic tests can reveal a much wider array of chromosomal abnormalities by examining all of the foetus’ genes for microdeletions and duplications. Holly Mueller, a genetic counsellor at the University of California, San Francisco, told HuffPost that such testing can screen for about 5,000 conditions. 

The advantage of the diagnostic tests is that the results are very accurate and can detect a large number of conditions. The cons are that they occur later in pregnancy, meaning that, depending on abortion restrictions in your state, you might have to travel to another state if you decide to terminate the pregnancy. In Florida, for example, abortion is banned after the 15th week of pregnancy.

There is also a small risk of miscarriage with either procedure. Mueller said that the risk of miscarriage with these tests is approximately 1 in 450 for CVS and 1 in 900 for amniocentesis. 

What testing will be available in the future?

A small study, involving 36 patients, was published in the New England Journal of Medicine in November. Researchers took a blood sample from each patient, as you would for a cell-free foetal DNA test, and then, using new technology known as “deep trio-exome sequencing,” they screened for a large number of genetic conditions, as you would with the sample taken from amniocentesis or a CVS test. This new test is referred to as the desNIPT test.

“The goal of the study is to see if can we do the same thing that we do on the invasive sample [CVS or amniocentesis] ... using a non-invasive test,” meaning the blood sample, Martin Larsen, one of the study’s authors, told HuffPost. 

The results showed that, using this new technology, the results from the desNIPT tests were just as accurate as the results from an amniocentesis. Larsen, a clinical laboratory geneticist at Odense University Hospital in Denmark, said there were no false positives in any of the patients involved in the study. There were a number of genetic diagnoses made, including a heart condition and dwarfism. The results of the blood tests were confirmed by CVS or amniocentesis on these patients (who were all considered high risk). That is, both tests — the blood test and the invasive test (CVS or amniocentesis) produced the same results. 

If further studies replicate this level of accuracy, desNIPT testing for many genetic conditions could become the norm in the first trimester of pregnancy. 

Pregnant people would be able to receive results earlier in pregnancy, in the first trimester (the cell-free foetal DNA test is currently offered as early as 10 weeks) — and without the risk, though small, of one of the invasive tests. 

Another significant advantage would be the ability to test for so many kinds of genetic conditions so early in the pregnancy. As it stands now, Larsen explained, patients are often referred for invasive testing after suspected abnormalities are seen on an ultrasound. 

“There’s a group of genetic diseases where you see malformations during pregnancies, and then there’s a very large group of genetic disorders that there’s no indication throughout the pregnancy that there is a problem.” In other words, there are many genetic disorders that won’t show up on an ultrasound — meaning the patient will not be referred for further testing.

“The potential is that this method can actually identify those pregnancies much earlier than what’s happening now,” Larsen said. 

In the report, the authors estimate a seven-day turnaround for patients to receive test results.

What are potential concerns about this new test?

More results earlier on sounds like a win-win. But there are a few areas of concern. 

The first is one of access. “One obstacle is the pricing of the test,” said Larsen.  “It’s pretty expensive for now.” The cell-free foetal DNA test is expensive, and the new desNIPT may be even more so. He hopes that further innovation will bring down the cost.

Mueller worries that in a country like the U.S. that does not guarantee health care, there may be wide disparities in who has access to the test. She said that she already sees income-based disparities in who has access to genetic testing — with higher-income people having diagnostic tests run more frequently — and a new, more expensive test could make disparities even greater. 

Mueller is also concerned about accuracy, as the recent study was small and there is a potential for error in test results.

“I would really be uncomfortable, at least at this point, with patients making reproductive decisions purely on the non-invasive results,” Mueller said. 

If any screening test was positive, she would still recommend that a patient have follow-up diagnostic testing to be more certain. Mueller did note that some patients in the United Kingdom are making reproductive decisions based on one currently available non-invasive test, but this is not common practice now in the U.S.

Another big difference between Europe and the U.S. is access to abortion care. Currently, 15 U.S. states have near-total bans on abortion, meaning that patients in those places need financial resources to travel for a procedure. For example, in a recent case in Texas, a woman whose foetus was diagnosed with trisomy 18 (a fatal condition) sued the state for access to an abortion and eventually left the state in order to terminate her pregnancy. 

For the time being, Mueller said, she asks the following questions of patients who are considering genetic testing: “Is it OK with you to potentially receive a result that’s going to muddy the waters a little bit more than clarify them? And are you willing to kind of take additional steps after we get that result to potentially get more information like diagnostic testing?”

“As long as you’re counselled appropriately, I’m all about patients getting testing that they feel is important and relevant to them.”