Estimation of Detection Rates of Aneuploidy in High-Risk Pregnancy Using an Approach Based on Nuchal Translucency and Non-Invasive Prenatal Testing: A Cohort Study

Abstract

Objectives: The aim was to investigate aneuploidy detection using an approach based on nuchal translucency (NT) and non-invasive prenatal testing (NIPT). Methods: This was a cohort study including 5,306 high-risk pregnancies with NT measurements and chorionic villus samples (CVS) tested for full karyotype. Results: The fetal karyotype was normal in 4,172 (78.6%) cases and abnormal in 1,134 (21.4%), including 1,009 with a likely clinically significant adverse outcome. Universal CVS with full karyotyping would lead to the diagnosis of all clinically significant abnormalities. A policy of relying solely on NIPT would have led to the diagnosis of 88.9% of clinically significant abnormalities. A strategy whereby NIPT is the main method, with CVS reserved for cases with NT ≥3.0 mm, would require CVS in 21.7% of cases, identify 94.8% of significant abnormalities and avoid miscarriage in 41 pregnancies compared to CVS for all. Conclusions: A policy of NIPT for increased-risk cases and CVS with full karyotype if the NT was ≥3.0 mm reduced the risk of miscarriage yet still identified 95% of clinically significant aneuploidy.

Nuchal translucency of 3.0‐3.4 mm an indication for NIPT or microarray? Cohort analysis and literature review

“…Based on the current data and literature review, we suggest that not only an NT ≥3.5 mm, but also an NT ≥3.0 mm could be considered as an indication for invasive prenatal testing because the frequency of chromosome aberrations seems to be very high (in the presented cohort 1:7.4 and according to the literature at least 1:14 7 ). Our results support the previous studies of both Khalil et al and Maya et al, who suggested that invasive testing should be offered in case of a fetal NT ≥3.0 mm 9,37 . If NIPT is offered as the first test, then these women may experience a longer period of anxiety (while waiting for a definitive result) because every abnormal NIPT result requires subsequent confirmatory diagnostic testing.…”

Chorionic villus sampling in the cell‐free DNA aneuploidy screening era: careful selection criteria can maximise the clinical utility of screening and invasive testing

“…33 Incorporating a NT threshold into the decision algorithm for invasive testing will reduce this proportion, with a recent cohort study demonstrating that when a CVS is prompted by either an abnormal cfDNA result or a NT of 3 mm or greater, only 5.2% of significant abnormalities would not be identified. 34 As noted earlier, our institutional policy is to offer a CVS when the NT is >3.5 mm. In this study, for those abnormal CVS results that would not have been detected by cfDNA testing, applying either this lower NT threshold of ≥ 3 mm or the local standard of 3.5 mm would have failed to identify only five pathogenic fetal karyotypic anomalies overall, representing 1.7% of all pathogenic CVS results in this series.…”

“…Studies that have utilised molecular karyotyping indicate that standard cfDNA testing alone would not identify up to 23.4% of potentially clinically significant karyotypic abnormalities that would otherwise have been identified by combined first trimester screening and invasive testing . Incorporating a NT threshold into the decision algorithm for invasive testing will reduce this proportion, with a recent cohort study demonstrating that when a CVS is prompted by either an abnormal cfDNA result or a NT of 3 mm or greater, only 5.2% of significant abnormalities would not be identified . As noted earlier, our institutional policy is to offer a CVS when the NT is >3.5 mm.…”

Has Noninvasive Prenatal Testing (NIPT) Come of Age?

“…The aim of a recent British study was to investigate aneuploidy detection using an approach based on nuchal translucency (NT) and noninvasive prenatal testing (NIPT) [10]. This was a cohort study including 5306 high-risk pregnancies with NT measurements and chorionic villus samples (CVS) tested for full karyotype.…”

“…This was a cohort study including 5306 high-risk pregnancies with NT measurements and chorionic villus samples (CVS) tested for full karyotype. A policy of NIPT for increased-risk cases and CVS with full karyotype if the NT was C3.0 mm reduced the risk of miscarriage, yet still identified 95 % of clinically significant aneuploidy [10].…”