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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).

Objective To evaluate the association between aberrant right subclavian artery (ARSA), with or without additional risk factors for aneuploidy or ultrasound abnormality, and results of chromosomal microarray analysis (CMA). Methods This was a multicenter study of fetuses diagnosed with ARSA that underwent genetic analysis by CMA, all samples being analyzed in the same laboratory. Clinical investigation included nuchal translucency measurement, first- and second-trimester maternal serum screening, early and late second-trimester fetal anatomy scans and fetal echocardiography. Comparative genomic hybridization microarray analysis or single-nucleotide polymorphism array technology was used for CMA of DNA samples obtained from amniotic fluid. Results CMA results were available for 63 fetuses with ARSA. In 36 fetuses, ARSA was an isolated finding, and no pathogenic variant was found. Additional ultrasound findings and/or risk factors for aneuploidy were present in 27 fetuses, five of which had pathogenic CMA results. Of these five, trisomy 21 was detected in a fetus with echogenic intracardiac focus (EIF), 22q11 deletion was detected in a fetus with EIF and an increased risk of trisomy 21 of 1:230 from maternal serum screening, 22q11 duplication was detected in a fetus with hypoplastic right kidney and choroid plexus cyst and 22q11 deletion was detected in a fetus with right aortic arch and clubfoot. The fifth fetus had increased nuchal translucency thickness (4 mm) and a ventricular septal defect, and CMA identified both 22q11 deletion and 1q21 duplication. Conclusions In fetuses with isolated ARSA, an invasive procedure for CMA is not indicated. However, CMA is recommended when additional ultrasound abnormalities or risk factors for aneuploidy are observed. The chromosomal findings in four of the five cases with an abnormal CMA result in our study would not have been detected by standard fetal chromosomal testing. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.