When noninvasive prenatal testing (NIPT) first became a reality nearly a decade ago, many involved in the care of pregnant women (clinicians and laboratorians alike) saw it as a game-changer. They thought the standard screening option for chromosomal abnormalities, maternal serum screening (MSS), would soon be obsolete. NIPT is a powerful test for Down syndrome and certain other chromosomal abnormalities with a high positive predictive value (PPV) This means there is a significantly lower false-positive rate, so it is likely that a positive result means the fetus actually has the condition. For example, QNatal® Advanced, Quest Diagnostic’s NIPT test, has an overall positive predictive value (PPV) for Down syndrome of 98.1%, with a false positive rate (FPR) of only 0.1%1. Compare that to the Quad screen or First Trimester screening, which have a PPV of less than 3% and an FPR of 5% for Down syndrome. Thus, NIPT can result in a significant decrease in the number of invasive prenatal diagnostic procedures (amniocentesis or chorionic villus sampling [CVS]) with a resulting reduction in procedural-related fetal losses. But this is not necessarily the end of the story.
What information can MSS provide?
MSS is a measurement of certain chemicals in a pregnant mom’s blood to assess a baby’s risk for Down syndrome and trisomy 18. It has been used to screen for open neural tube defects (ONTD) since the 1970’s, Down syndrome since the 1980’s, and trisomy 18, since the 1990’s. In addition to Down syndrome and trisomy 18, other atypical chromosome abnormalities may be serendipitously ascertained with a screen positive MSS. For example, a woman with a screen positive for Down syndrome or trisomy 18 may have a fetus with a different, less common chromosome abnormality. In fact, one study found that abnormal first trimester screens identified 55% of such unusual chromosome abnormalities2. Some physicians use the MSS biochemical levels to independently screen for pregnancies at risk for complications such as pre-eclampsia, low birth weight, preterm delivery, or fetal demise. AFP (alpha fetoprotein) is measured as part of MSS and is a key predictor of spina bifida, regardless of a concern for chromosome abnormalities.
What information can NIPT provide?
NIPT is also a blood test, looking at DNA from the placenta to assess a fetus’s risk for certain chromosome abnormalities. Some providers routinely offer NIPT, and if the results are abnormal, follow-up diagnostic testing is offered. It is important to counsel patients that NIPT will not identify all chromosome abnormalities. This is especially significant for younger women (less than 36 years of age) as they have a higher risk for these less common chromosome abnormalities than for Down syndrome3. ACOG recently recommended that NIPT should be offered to pregnant patients regardless of age3. MSAFP for ONTD’s should be ordered in the second trimester, as NIPT does not screen for these.
Some providers offer MSS, with follow-up testing of either NIPT or proceeding directly to diagnostic testing following screen positive results. If a patient with a screen positive MSS opts for NIPT as the follow-up test, she should be counseled that a normal NIPT result has a residual risk of about 2% for an atypical chromosome abnormality3. Fetal diagnostic testing (CVS or amniocentesis) with microarray will identify aneuploidies as well as atypical chromosome abnormalities. But not all patients choose these invasive tests, perhaps due to the small risk for pregnancy loss.
So, what then is a clinician to do regarding non-invasive screening? NIPT? MSS? Patients should be counseled about their risk for chromosomal abnormalities, and also the benefits and limitations of MSS, NIPT, as well as amniocentesis, and CVS. Some patients prefer going directly to diagnostic testing. Others, wishing to avoid an invasive test, may choose NIPT or MSS. And of course, some patients will decline all testing based on their personal convictions. Patients make informed choices based on these discussions, their own clinical situation, the medical resources available to them, and their personal principles and beliefs. An online resource for patients and providers about these tests and conditions is https://www.lettercase.org/. Furthermore, genetic counseling prior to testing is an option for patients who are clearly undecided.
We’ve certainly come a long way since the early 1980’s. The only screening test available then was maternal age, and the only diagnostic test was amniocentesis with a karyotype. Now we have a plethora of MSS tests, NIPT, CVS and amniocentesis with karyotyping and/or microarray at our disposal. Just like at the paint store, more choices are great. But it sure makes choosing even more difficult! More information about Quest’s prenatal screening offerings can be found athttps://www.questdiagnostics.com/home/patients/health-test-info/womens-health/prenatal/during-pregnancy/ or speak to a genetic counselor at 1.866.GENE INFO (1.866.436.3463).
- Guy C, Haji‐Sheikhi F,Rowland CM, et al. Prenatal cell‐free DNA screening for fetal aneuploidy in pregnant women at average or high risk: Results from a large US clinical laboratory. Mol Genet Genomic Med. 2019;e545. https://doi.org/10.1002/mgg3.545
- Iwarsson E, Conner P. Detection rates and residual risk for a postnatal diagnosis of an atypical chromosome aberration following combined first-trimester screening. Prenatal Diagnosis. 2020;40:852-859. https://doi.org/10.1002/pd.5698
- Screening for fetal chromosomal abnormalities. ACOG Practice Bulletin No. 226. American College of Obstetricians and Gynecologists. Obstet Gynecol 2020;136.