[Analysis of copy number variation by CMA in fetus with increased nuchal translucency]

Objective: To investigated the clinical value of chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) . Methods: Totally 101 cases out of 19 261 singleton fetuses who underwent the first trimester (11-13⁺⁶ weeks) ultrasound examination from January 2015 to June 2017 at First Affiliated Hospital of Sun Yat-sen University were diagnosed with NT ≥2.5 mm and underwent invasive prenatal test for fetal karyotype and CMA. According to the combination of other ultrasound abnormalities, the cases were divided into isolated group (67.3%, 68/101) and complicated group (32.7%, 33/101) . In addition, the cases were divided into 5 groups according to the thickness of NT, 2.5-2.9 mm (borderline thickening; 16.8%, 17/101) , 3.0-3.4 mm (33.7%, 34/101) , 3.5-4.4 mm (16.8%, 17/101) , 4.5-5.4 mm (15.8%, 16/101) , and ≥5.5 mm (16.8%, 17/101) . Chi square test was used to detect the different rates of other combined ultrasound abnormalities and abnormal chromosome between 5 groups. Results: The median thickness of NT was 3.4 mm (2.5-8.5 mm) . And 32 cases (31.7%, 32/101) had abnormal karyotype. There was a significant difference in the frequency of abnormal karyotype between the isolated and the complicated group (20.6% vs 54.5%, P<0.01) . Among 69 cases (68.3%, 69/101) of normal karyotype, 3 cases (4.3%, 3/69) were detected with pathogenic copy number variation (CNV) by CMA. Thirty-five cases with chromosomal abnormalities (include abnormal karyotype and pathogenic CNV) , there was a significant difference in the frequency of chromosomal abnormalities between the isolated and the complicated group (23.5% vs 57.6%, P=0.001) . The median age of pregnant women in 5 groups was 35 years (24-39 years) , 33 years (23-46 years) , 31 years (21-46 years) , 33 years (21-41 years) and 35 years (21-43 years) . The rates of chromosomal abnormalities increased with the increase of NT thickness. There was significant difference in the incidence of associated chromosomal abnormalities among 5 groups (P<0.05) . Comparative analysis within the 5 groups, the incidence of associated chromosomal abnormalities between NT 2.5-2.9 mm and ≥5.5 mm was significantly different (P=0.005) , while the differences between the other groups were not significant (P>0.05) . Conclusions: There is a high risk of fetal chromosomal abnormalities in borderline NT thickening (2.5-2.9 mm) at advanced maternal age, but the pathogenic CNV is not detected. Chromosomal microdeletion or microduplication could be further detected in the NT thickening (≥3.0 mm) fetuses with normal karyotype by chromosome microarray analysis, while the positive rate is relatively low, and the variants of unknown significance might be detected.