Tanya just found out she’s pregnant for the first time. She walks into her doctor’s office nearly in tears having gotten to her appointment early and had time to read all of the brochures in the waiting room. “I want a healthy baby. Test me for everything!” she tells her doctor. In reality, like many women and couples, she’s probably feeling overwhelmed by the amount of information and number of testing options now available in the preconception and prenatal period.
Tanya is not alone; her doctor may be feeling similarly overwhelmed by the available testing options. The goal of preconception and prenatal testing is to give providers and patients information about genetic risks that can help decision-making. In recent years the options for prenatal and preconception testing have grown significantly. As our understanding of the genetic make-up of disease has increased, technology has made genetic testing quicker, more accurate, and less expensive.
Expanded carrier screening allows a couple to learn their risks for having a child with 100 or more rare genetic conditions. After becoming pregnant, cell free DNA screening (also called Noninvasive Prenatal Testing or NIPT) can determine the likelihood of a fetus being affected by a chromosome abnormality, such as Down syndrome, more accurately and safely than ever before simply by taking a sample of blood from Mom. While all health care decisions are individual, those around pregnancy are particularly fraught with emotional and ethical issues. The same amount of information welcomed by one couple may increase the anxiety of another.
As has always been the case in the prenatal space, facilitating decision-making means balancing the information available through testing with the needs of the woman or couple. Providers can help couples navigate the testing options and identify the right approach for their needs. However, patients and providers may have misconceptions about the capabilities of new tests, which should be addressed before decision-making.
Common misconceptions about test capabilities
Negative results from both expanded carrier screening and cell free DNA screening can be reassuring, but no testing can completely rule out genetic disease. These tests look for specific types of genetic conditions; there is no test that assesses for all genetic conditions. Carrier screening usually screens for rare, recessive conditions, while cell free DNA screens for common chromosome conditions.
In addition, both are screening tests, not diagnostic. While these screening tests are safe because they are not invasive, they are not definitive. For couples who are uncomfortable with uncertainty, no screening test may be right for them because it won’t give them a definite answer, though it may help determine whether to go on to more invasive tests.
Pre- and post-test counseling is critical. Before testing, women and couples should understand the limitations of available testing and implications of negative or positive results in order to facilitate informed decision-making.
Carrier screening is not diagnostic testing. Results provide information about an individual’s or couple’s risk of having an affected child. In the past, carrier screening has been limited to a highly curated set of conditions within specific populations, such as sickle cell disease in African Americans and Tay Sachs disease in Ashkenazi Jewish individuals, and typically included only conditions that are very severe. The original screening criteria were established in part to make the best use of resources in an era when genetic testing was expensive and time consuming. Now, expanded panels include conditions that don’t meet those original criteria. These panels can include conditions with a variety of outcomes, including those that don’t have onset until adulthood and/or have less severe symptoms. Some laboratories allow customization of the panel, such that specific conditions or categories of disease can be excluded.
Professional guidelines currently support cell free DNA screening for women at increased risk of having a child with a chromosome condition. Being over 35 years of age, having a family history of a chromosome condition or multiple miscarriages, and having abnormal results on other prenatal testing all put a woman at increased risk. For women at increased risk, cell free DNA has better detection for common chromosome conditions (Down syndrome/trisomy 21, trisomy 18, trisomy 13, and sex chromosome conditions) than other prenatal screening options, such as maternal serum screening.
For women at average or low risk, however, the chance for a false positive is significantly greater than in the high risk population. The test is less predictive because the chance that a positive result is accurate on any test (positive predictive value) is based, in part, on how frequent the condition occurs in the population. The prevalence of Down syndrome is lower for younger women than women over 35 years of age, so the test does not perform as well in that population.
As technology continues to expand our ability to provide risk information, the discussion of the benefits and limitations of different tests in the context of the couples’ expectations and needs becomes increasingly important. Professional societies and experts in the field have offered specific key points to be incorporated into counseling about expanded carrier screening and cell free DNA screening.
For more education about expanded carrier screening and cell free DNA screening, here are some quality resources.
The value of family history in the prenatal care practice: A slide-set for educators on the value of family history in general prenatal care that focuses on family history collection and interpretation in prenatal case studies.
Sachs A, Blanchard L, Buchanan A, Norwitz E, Bianchi DW. Recommended pre-test counseling points for noninvasive prenatal testing using cell-free DNA: a 2015 perspective. Prenat Diagn. 2015 Oct;35(10):968-71.
Edwards JG et al. 2015. Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstetrics & Gynocology. 125(3):653.