2.1 Estimation of detection rates of aneuploidy using an approach based on nuchal translucency and non-invasive prenatal testing (NIPT)

Abstract

Objectives To investigate the detection rates of aneuploidy using nuchal translucency (NT) and non-invasive prenatal testing (NIPT). Methods A retrospective cohort study including 5306 pregnancies that underwent chorionic villus sampling (CVS) for full karyotyping after fetal NT measurement at 11+0–13+6 weeks of gestation. All abnormal karyotypes were reviewed by a clinical geneticist and grouped according to whether the chromosome anomaly would be detectable by NIPT and whether it might be clinically significant. Results The fetal karyotype was normal in 4172 (78.6%) and abnormal in 1134 (21.4%), including 1009 likely to result in clinically significant adverse outcome. Universal CVS with full karyotyping would lead to the diagnosis of all clinically significant abnormalities. A policy of NIPT only in all of these cases would have led to the diagnosis of 88.9% of clinically significant abnormalities. A strategy whereby NIPT is the main method of analysis for increased combined screening risk, with invasive testing reserved for those with NT thickness ≥3.0 mm, would require CVS in 20.1%, identify 94.8% of significant abnormalities and avoid miscarriage in 42 (79.2%) pregnancies compared to CVS for all. With a current UK price for NIPT of £400 and the need to confirm abnormal results by CVS, the cost of the three policies would be £2.0 m, £2.5 m and £2.2 m, respectively. Conclusions A policy of NIPT for increased first trimester aneuploidy risk and CVS with full karyotype only for fetal NT thickness ≥3.0 mm would reduce the risk of procedure-related miscarriage five-fold, yet identify 95% of clinically significant chromosomal abnormalities.

Should cell‐free DNA testing be used in pregnancy with increased fetal nuchal translucency?

“…This rate is higher than that observed by Lichtenbelt et al . (11%) or in the French multicenter study (12%); while the respective rate varies in large series including high‐risk fetuses, from 11% in the study of Khalil et al ,. to 21% in a study from the FMF.…”

“…In our study, 19% (16/84) of all genetic anomalies identified in fetuses with an enlarged NT were not trisomies 13, 18 or 21. This rate is higher than that observed by Lichtenbelt et al 11 (11%) or in the French multicenter study 23 (12%); while the respective rate varies in large series including high-risk fetuses, from 11% in the study of Khalil et al 25 , to 21% in a study from the FMF 26 .…”

Detection of fetal chromosomal anomalies: does nuchal translucency measurement have added value in the era of non‐invasive prenatal testing?

“…Khalil et al reported that in 5306 pregnancies with an increased NT, 24% had a chromosomal anomaly at CVS, of which 11% were not trisomy 13, 18, or 21. Syngelaki et al detected an abnormal karyotype in 13.8% of 14 684 pregnancies with an increased NT, of which 20.8% were anomalies other than trisomies 13, 18, and 21 . Petersen et al reported 11% abnormal karyotypes in 10 205 pregnancies after abnormal FCT results, of which 38.6% were a chromosomal anomaly other than trisomies 13, 18, and 21.…”