The role of whole-exome sequencing (WES) in evaluating fetuses with increased nuchal translucency (NT) remains debated, particularly after normal chromosomal testing. In this large retrospective cohort, chromosome microarray analysis (CMA) identified chromosomal abnormalities in nearly one-fifth of fetuses with NT ≥3 mm, with significantly higher detection rates in those with additional ultrasound anomalies. Among fetuses with NT ≥3.5 mm and negative CMA results, WES provided an incremental diagnostic yield of 10.42%, identifying pathogenic variants in genes associated with syndromic and neurodevelopmental disorders, most of which were linked to adverse pregnancy or postnatal outcomes.
Importantly, the majority of fetuses with isolated increased NT and negative genetic testing demonstrated normal long-term outcomes. These findings support a stepwise genetic testing strategy, reserving…
