Miranda J, Mino FPY, Borobio V, et al. - This study was undertaken to investigate the frequency of atypical chromosomal and submicroscopic anomalies, as well as fetal structural abnormalities, determined on first‐trimester ultrasound scan in fetuses with nuchal translucency (NT) thickness > 99th centile, in order to assess the suitability of applying standard cell‐free DNA (cfDNA) testing as the sole screening test in these pregnancies. A retrospective cohort study was conducted to include 226 fetuses with NT > 99th centile at 11–14 weeks' gestation, between January 2013 and December 2017, in a clinical setting in which greater than 95% of pregnant women receive first‐trimester combined screening. Researchers evaluated the theoretical yield of two cfDNA testing models, targeted cfDNA (chromosomes 21, 18 and 13) and extended cfDNA (chromosomes 21, 18, 13 and sex chromosomes), and matched it with that of cytogenetic testing and ultrasound evaluation in the first and second or third trimesters. This study's findings demonstrate that, in fetuses with NT > 99th centile, cfDNA does not seem to be the appropriate genetic test, given that it would miss 12–19% of genetic anomalies in this group. A major structural abnormality in 11% of the fetuses with NT > 99th centile and no genetic anomaly will bee identified by first‐trimester ultrasound.