Genetic Counseling Corner
Noninvasive Prenatal Testing: Understanding the Importance of Proper Interpretation and Genetic Counseling
Noninvasive prenatal testing (NIPT), also referred to as noninvasive prenatal screening (NIPS), has drastically changed the landscape of prenatal testing and offers tremendous potential as a screening tool for fetal aneuploidy. This option first became available through one laboratory in the U.S. in late 2011 as a screen for trisomy 21. Since then, this type of screening has rapidly expanded and is now available through numerous laboratories across the country for multiple chromosomal abnormalities. While most are in agreement that NIPT has advantages over the more traditional serum screening, there is much to consider with regard to interpretation of results and counseling families both before and after testing.
Studies conclude NIPT has increased sensitivity, specificity and positive predictive value over both first trimester screening and second trimester serum screening; however, it is imperative that practitioners and patients alike recognize NIPT is a screening tool and is not diagnostic. NIPT has been advertised and extensively marketed as a highly accurate test and is frequently described as being over 99 percent accurate. While the sensitivity and specificity of NIPT are frequently greater than 99 percent, the positive predictive value is almost always less than 99 percent. Counseling patients about the meaning of NIPT results can be complicated; therefore, clear explanations of sensitivity, specificity and positive predictive value are essential.
Sensitivity–the proportion of affected pregnancies that will screen positive.
“What are the chances this test will detect Down syndrome if it is present?”
Specificity–the proportion of unaffected pregnancies that will screen negative.
“What are the chances I will get a reassuring result if my pregnancy does not have Down syndrome?”
Positive Predictive Value–the proportion of positive test results that are true positives.
“What are the chances that my positive NIPT result actually means my pregnancy has Down syndrome?”
When interpreting abnormal results and counseling patients about the meaning of such results, positive predictive value (PPV) is perhaps the most meaningful number for patients to understand. PPV takes into account not only sensitivity and specificity of the screening test, but also the prevalence of the condition. Prevalence depends on many factors, such as the genetic condition, maternal age, gestational age and ultrasound results. As the use of NIPT expands to low-risk populations and less prevalent chromosome conditions, the impact of prevalence on PPV will become more evident. Therefore, while performance of NIPT is impressive in both high-and low-risk populations, counseling about abnormal results will be different for each individual patient
based on their a priori risk for the condition.
For example, interpretation of abnormal NIPT results for Down syndrome differs for a 40-year-old woman versus a 20-year-old woman. The PPV for the 40-year-old woman is higher (91 percent) than the PPV for the 20-year-old woman (50 percent). Given the lower prevalence of Down syndrome in younger women, the PPV in this population is lower, resulting in a higher number of false positive results in this population. Therefore, the genetic counseling for these two patients is different despite them both having a “positive” NIPT for Down syndrome. See figures on the following page.
The American Congress of Obstetricians and Gynecologists (ACOG) recommends all women be offered screening for aneuploidy during pregnancy. Screening with increased sensitivity, specificity and PPV is ideal; however, it is important to note for some families, screening is not desired. Pre-test counseling is essential for patients to understand the benefits and limitations of their screening options and aids in informed decision-making and anticipatory guidance regarding follow-up recommendations. Additionally, genetic counseling for detailed interpretation of results and options for diagnostic testing is recommended for all women with abnormal screening results.