Increased nuchal translucency with normal karyotype and genomic microarray analysis: A multicenter observational...

Area of Science:

• Prenatal diagnosis
• Fetal medicine
• Genetics

Background:

• Increased nuchal translucency (NT) is a marker for adverse fetal outcomes.
• Genetic testing (karyotype and array-CGH) and mid-trimester anomaly scans are standard in evaluating fetal NT.
• The residual risk of morbidity in fetuses with isolated increased NT after these tests requires further definition.

Purpose of the Study:

• To determine the residual risk of morbidity-related outcomes in fetuses with nuchal translucency (NT) of 3.5 mm or greater.
• To assess this risk after normal genetic testing (karyotype and array-CGH) and a normal mid-trimester anomaly scan, including RASopathy testing.

Main Methods:

• A cohort of 114 fetuses with isolated NT ≥ 3.5 mm and normal karyotype/array-CGH was studied.
• Fetuses were grouped by NT size: 3.5-4.5 mm, 4.5-6 mm, and >6 mm.
• Outcomes evaluated included genetic disorders, structural abnormalities, pregnancy, and long-term pediatric results following genetic and ultrasound assessments.

Main Results:

• Initial residual risk of morbidity was 24.64% (NT 3.5-4.5 mm), 25% (NT 4.5-6 mm), and 76.47% (NT >6 mm) after normal karyotype/array-CGH.
• Following normal RASopathy testing and mid-trimester scan, residual risks reduced to 7.14%, 8.69%, and 33.3% in the respective NT groups.
• The risk of adverse outcomes is directly correlated with NT size.

Conclusions:

• Fetal morbidity risk in isolated increased NT depends on NT size, even after normal genetic testing.
• While normal RASopathy testing and mid-trimester scans are reassuring, the residual risk of poor outcomes remains higher than in the general population.
• Particular caution is advised for fetuses with NT greater than 6 mm due to significantly increased residual risk.