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.

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.