Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency

Area of Science:

• Prenatal diagnostics
• Genetics
• Fetal medicine

Background:

• Increased nuchal translucency (NT) is a significant ultrasound finding associated with various fetal chromosomal anomalies.
• Accurate and comprehensive genetic testing is essential for managing pregnancies with increased NT.

Purpose of the Study:

• To compare the diagnostic yield of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) for chromosomal anomalies in fetuses with isolated increased NT.
• To evaluate the utility of NIPT in cases of increased NT and to assess the role of CMA and karyotyping.

Main Methods:

• Retrospective study of 249 fetuses with increased NT or cystic hygroma (≥3.5 mm) as an isolated sign.
• Analysis of karyotype, fluorescence in situ hybridization (FISH), and CMA results obtained between 11 and 18 gestational weeks.

Main Results:

• Karyotype and FISH detected 103 chromosomal anomalies, including 95 aneuploidies and 8 rearrangements.
• CMA identified additional pathogenic or likely pathogenic copy number variants (CNVs) and variants of unknown significance (VOUS) in fetuses with normal karyotypes.
• NIPT failed to detect over 15% of anomalies identified by invasive techniques, highlighting its limitations in this context.

Conclusions:

• NIPT is not recommended for isolated increased NT due to its limited detection rate for chromosomal anomalies.
• CMA is valuable as a second-tier test after rapid aneuploidy screening for fetuses with increased NT.
• Karyotype analysis remains important and should not be dismissed in the evaluation of increased NT.