Prenatal Blood Tests For Down Syndrome Good But Not Perfect

Jeanne M. Meck, PhD FACMG Director, Prenatal Diagnosis & Cytogenomic GeneDx Gaithersburg, MD Interview with:
Jeanne M. Meck, PhD FACMG
Director, Prenatal Diagnosis & Cytogenomic
Gaithersburg, MD 20877

Medical Research: What is the background for this study?

Dr. Meck: Non-invasive prenatal screening (NIPS) for fetal aneuploidy is a new test which requires only a blood sample from the pregnant mother to provide a risk estimate of whether or not her fetus has a chromosomal aneuploidy such as trisomy 21 (Down syndrome), trisomies 13 or 18, or a sex chromosome abnormality. This testing relies on the fact that circulating maternal blood contains cell free fetal DNA. Published studies have reported very high specificities and sensitivities. However, the more important question is what is the positive predictive value (PPV= #true positive results/#true positive + false positive results) since it answers the question of interest to physicians and patients: “Given an Non-invasive prenatal screening result that shows a high risk for a given fetal aneuploidy, what is the chance that the fetus is affected?” We attempted to answer this question by looking at the results of fetal chromosome analyses on chorionic villus samples (CVS) or amniotic fluid that were referred to our cytogenetics laboratories after Non-invasive prenatal screening in order to see if NIPS correctly predicted the fetal karyotype.

Medical Research: What are the main findings?

Dr. Meck: When comparing Non-invasive prenatal screening results to diagnostic cytogenetic testing (chromosome analysis or chromosomal microarray), we found that 69% of the positive NIPS results (129/186) were true positive, while 96% (25/26) of the negative NIPS results were true negative. We found the PPV for trisomy 21 to be the highest at 93%. The PPVs for the other aneuploidies were much lower: trisomy 18 –58%; trisomy 13–45%; monosomy X–23%.

Medical Research: What should clinicians and patients take away from your report?

Dr. Meck: The positive predictive values show that while a positive Non-invasive prenatal screening test result for trisomy 21 is likely to accurately predict a trisomy 21 fetus, positive Non-invasive prenatal screening results for the other aneuploidies examined do not correlate as well with the true fetal karyotype. This is due, in part, to the higher prevalence of trisomy 21 than the other aneuploidies. It is very important to remember that Non-invasive prenatal screening is a screening test, not a diagnostic test. Any positive findings suggesting a high risk for a chromosomal aneuploidy needs to be followed up by diagnostic testing such as chromosome analysis or chromosomal microarray performed on CVS or amniotic fluid. Furthermore, negative NIPS results do not mean that the chance of a chromosome abnormality in the fetus has been completely ruled out.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Meck: More studies assessing the PPV of the various aneuploidies are needed to get a larger sample size and, therefore, more accurate determination of the PPV for each aneuploidy. Furthermore, although Non-invasive prenatal screening is the best screening test to date for fetal aneuploidy detection, more studies need to be performed to understand the maternal and or pregnancy-related situations in which a false positive or false negative result occurs.


Non-Invasive Prenatal Screening for Aneuploidy: Positive Predictive Values Based on Cytogenetic Findings

Meck, Jeanne M. et al.

American Journal of Obstetrics & Gynecology

Received: January 20, 2015; Received in revised form: March 13, 2015; Accepted: April 1, 2015; Published Online: April 02, 201 Interview with: Jeanne M. Meck, PhD FACMG (2015). Prenatal Blood Tests For Down Syndrome Good But Not Perfect