Chorionic Villus Sampling, Early Amniocentesis, and Termination of Pregnancy Without Diagnostic Testing: Comparison of Fetal Risk Following Positive Non-invasive Prenatal Testing

Background: With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen. Method: Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure useddthat is, CVS, EA, or termination of pregnancy (TOP). Results: Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs. Conclusion: CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing.