# Diagnostic Value of Karyotype, Microarray, RASopathy Gene Testing and Ultrasound in Fetuses with Nuchal Translucency 3.0–3.4 mm: A Single-Center Cohort Retrospective Study

## TL;DR

This study shows that fetuses with a nuchal translucency of 3.0–3.4 mm have a high risk of genetic issues and birth defects, suggesting the need for detailed genetic and ultrasound testing.

## Contribution

The study demonstrates the added diagnostic value of advanced genetic testing and detailed ultrasound in fetuses with mildly increased nuchal translucency.

## Key findings

- Genetic abnormalities were detected in 28.9% of cases, with five rare anomalies identified only through advanced testing.
- Major structural malformations occurred in 17.5% of cases, with nearly 60% linked to genetic abnormalities.
- Advanced genetic testing provided an additional diagnostic yield of 3.1% in the cohort.

## Abstract

Background: Increased nuchal translucency (NT) is associated with an elevated risk of genetic abnormalities and structural malformations. The clinical utility of invasive testing and the optimal diagnostic approach in mildly increased NT (3.0–3.4 mm) is debated. This study aimed to evaluate genetic and ultrasound findings in this subgroup and to assess the diagnostic yield of advanced genetic testing. Methods: We retrospectively included a total of 107 fetuses with NT between 3.0 and 3.4 mm from a single fetal medicine unit. Complete outcome data were available for 97 pregnancies. Invasive prenatal testing with standard karyotype, chromosomal microarray analysis (CMA) and RASopathy panel testing were offered. All patients underwent detailed ultrasound examination to detect structural abnormalities at 16 and 20 weeks, regardless of whether invasive testing was performed. Results: Invasive prenatal testing, amniocentesis or chorionic villus sampling, (CVS), was performed in 77/97 cases (79.4%). Genetic abnormalities were detected in 28/97 (28.9%). Overall, five rare genetic anomalies were identified; none would have been detected by quantitative fluorescent polymerase chain reaction (QF-PCR) or non-invasive prenatal testing (NIPT). Two anomalies were detectable by standard karyotype, two exclusively by CMA and one exclusively by RASopathy panel. When considering all cases undergoing advanced genetic testing (CMA or RASopathy panel, n = 35) the overall diagnostic yield was 8.5% (3/35). When calculated across the entire cohort with complete follow-up, the additional diagnostic yield was 3.1% (3/97). Major structural malformations were identified in 17/97 cases (17.5%), of which 10 (58.8%) were associated with genetic abnormalities. Conclusions: Fetuses with NT measurements between 3.0 and 3.4 mm show a substantially increased risk of genetic abnormalities and structural malformations. These findings support a comprehensive prenatal evaluation, including invasive testing with advanced genetic analysis and detailed ultrasound assessment, to optimize diagnosis and counseling.