In addition to being a Mama Coach, I have practiced for several years as a pediatric nurse practitioner in genetics at multiple academic hospital centers. In the course of this practice, each year I meet hundreds of families and their new babies who are suspected of being affected by a genetic disorder. All too often, a palpable sense of confusion and anger are understandably demonstrated by the parents of these children—“We’ve had normal genetic testing,” they tell me, “how is this possible?”
This scenario is by no means unique, and with the proliferation of genetic testing options and a marked increase in genetic testing accessibility, it is becoming more common each year. So how is this possible? In short, patients who have undergone genetic testing without the benefit of counseling by a certified genetic counselor, genetic nurse practitioner, or medical geneticist may not fully understand what it was they have been tested for, or what their results actually mean. The consequence is often a false sense of assurance regarding the possibility of a genetic disorder occurring, and in cases where the question of a genetic disorder is eventually raised, devastating psychological effects can be experienced by these families.
What is Prenatal Genetic Testing?
In short, prenatal genetic testing is testing specifically undergone prior to the birth of a child with the goal of either determining overall risk for certain chromosomal abnormalities and a select few other genetic disorders; or in some cases, diagnosing these chromosomal abnormalities and some select disorders in-utero.
Prenatal genetic testing is not an overall survey of a fetus’s genetics. There are approximately 30,000 genes in the human genome which form the basic instruction manual for how we function and who we are. The vast, vast majority of these genes and the disorders potentially associated with them will never be looked at prenatally. Instead, prenatal genetic testing focuses mostly on “big picture” genetics: how much genetic material is present, and whether any large pieces may be missing or duplicated.
Similarly, carrier screening performed by commercial labs (think 23 and Me) or as part of the IVF process usually cover only a small percentage of genes. So while your commercially-procured genetic screening report may indicate that you are not a carrier for any disease, in reality this result means that you are not a carrier for any of the most common, known variants in the handful of genes that were tested. Big difference, right?
What different types of Prenatal Genetic Testing are Available?
Prenatal genetic testing generally falls under two distinct categories: screening tests and diagnostic tests. The purpose of a screening test is to give parents valuable information regarding the probability or likelihood that the child they are carrying or plan to carry might be affected by various chromosomal abnormalities (sometimes called aneuploidies) and a select few other genetic disorders which a particular screening test may be capable of targeting. Parental carrier screening tests, Non-Invasive Prenatal Testing (NIPT), and traditional combined methods of first and second trimester screening (which use both specific markers in Mom’s blood as well as measurements from ultrasound imaging to calculate a risk score) all fall under the “screening” umbrella. There are some key factors which are essential to understand about all screening tests:
1. These tests are not diagnostic in nature. Receiving an abnormal or “high risk” screening report does not mean your unborn child has been diagnosed with a particular disorder. Generally, receiving such a report would necessitate diagnostic testing to be completed.
2. Not all screening tests are created equal. The accuracy, cost, and clinical value of screening tests varies widely.
The purpose of a diagnostic test is tell parents whether the child they are expecting is actually affected by certain disorders. These tests are performed by collecting a sample of cells directly from the fetus, amniotic fluid, or placenta. Prenatal diagnostic genetic testing includes amniocentesis and chorionic villis sampling (CVS). While the accuracy of diagnostic testing is its clear benefit, an important consideration for these testing methods, even when recommended by your care provider in the context of an abnormal screening test, is a slight risk of miscarriage. This risk varies by test and personal factors related to the pregnancy, but is now thought to be much lower (approximately 1 in 1000) than previous estimates (1 in 200). This is largely because the estimates of higher risk were generated prior to the regular use of ultrasound imaging to guide the collection of cell samples.
Who is Prenatal Genetic Testing Available to?
Some form of prenatal genetic screening test is offered to every woman in the United States and Canada. Which screening test(s) are offered is highly dependent on insurance coverage, past medical history, the outcome of previous pregnancies, and a care provider’s assessment regarding the risk-level of a specific pregnancy. Women may have the opportunity to pursue additional screening tests, including the NIPT, by opting to pay out-of-pocket. Be sure to ask your care provider’s office which screening tests they offer, and if they can assist in facilitating a particular type of screening test you might be interested in, even if the cost of the test will not be covered.
How Accurate are Different Prenatal Genetic Testing Methods?
Parents’ (and obstetricians’ and midwives’) understanding of the accuracy of various prenatal genetic testing/screening methods is often where the testing process can go awry. Of the various testing methods available, the diagnostic tests are certainly the most accurate. However, due to their comparatively invasive nature and the slight risk of miscarriage associated with CVS or amniocentesis, these are often not considered the “best” testing options. Further, in the United States and Canada they are rarely considered “first line” testing options—they are most often considered following a high risk screening result, and therefore are not offered to most women.
Accuracy of screening methods was improved substantially following the introduction of NIPT, which is quickly becoming the go-to screening test for many families due to its increasing accessibility and ability to detect the sex of a baby in the first trimester. A word of extreme caution here—despite what your cousin, best friend, or a company’s marketing materials may have told you, the commonly repeated and generally accepted knowledge that these tests are “99.9% accurate” is only part of the story. Depending on the specific laboratory/company offering the test, this figure generally refers to a screening test’s ability to determine a true negative result, or a test’s negative predictive value (NPV). In other words, this figure captures the likelihood a result says “low risk,” and the child is truly not affected. Conversely, data regarding NIPT’s true positive results, or their positive predictive values (PPV), can vary significantly. One of the most popular NIPTs routinely offered in the United States, which is commonly spoken about as being 99% accurate, in actuality reports PPVs as high as 91% for trisomy 21 (Down syndrome), and as low as 5% for Prader-Willi syndrome. What do these numbers mean? As an example, in the case of Turner Syndrome, which has a reported PPV of 50% on this test, a fetus is only truly affected by Turner syndrome in 50% of the instances in which a parent receives a report that their baby is considered to have a “high risk” of this disorder. Further, accuracy of test results for screening panels, including the NIPT, can vary substantially depending on when in a pregnancy the test was drawn, the amount of fetal DNA present in the mother’s blood, the age of the mother, and whether or not the pregnancy is singleton.
What is the Best Way to Understand My Results? While obstetricians and midwives have an abundance of knowledge regarding their particular specialties and are more than qualified in guiding women and families through the pregnancy and childbirth experience—keep in mind that genetics is not their medical specialty, and is outside the realm of their expertise. To get the most out of any genetic testing or screening result, always speak to a certified genetic counselor, genetic nurse practitioner, medical geneticist, or maternal-fetal medicine specialist (who often also complete additional training and fellowships in genetics). The good news is these professionals are relatively accessible to you if you have recently undergone genetic screening or testing—ask your care provider for an appropriate referral. If you have qualified for or opted for NIPT, all laboratories that offer these tests also offer free consultation with a genetic counselor to review your results with you. Never be afraid to lean on these professionals on your road to empowered parenthood—you’ve got this, Mama.