The cut-off value for normal nuchal translucency evaluated by chromosomal microarray analysis

Objectives An association between isolated, increased nuchal translucency thickness and pathogenic chromosomal microarray analysis (CMA) has been reported. A recent meta-analysis reported that most studies used a 3.5 mm cut-off value. Considering nuchal translucency distribution and the commonly accepted 5% false positive rate in maternal serum screening, nuchal translucency cut-off levels should be reconsidered. This study evaluated the unique contribution of CMA to the investigation of foetuses with mildly increased nuchal translucency (NT) thickness of 3.0-3.4 mm. Methods This was a retrospective, multicenter study. A single laboratory performed all genetic analyses. Comparative Genomic Hybridization Microarray analysis or Single Nucleotide Polymorphism Array technology was used for CMA. NT was divided into three groups (≤2.9; 3.0-3.4; ≥3.5 mm) and the results were compared, focusing on pregnancies with NT as the only medical indication for CMA at the time of the invasive procedure. If combined first trimester screening (NT and biochemistry) indicated increased risk for common aneuploidies, the case was excluded. Results CMA results were recorded in 1,588 pregnancies, of which 770 foetuses had NT as a normal or an isolated abnormal finding. Of these, 462 had NT ≤2.9 mm, 170 had NT 3.0-3.4 mm and 138 had NT ≥3.5 mm. Pathogenic copy number variations were found in 1.7%, 7.1%, and 13.0%, respectively. Conclusions The results suggest that CMA should be part of the investigation in foetuses with isolated, mildly increased NT (3.0-3.4 mm).