Diagnostic value of karyotyping, CMA/CNV-seq, and WES in fetuses with thickened nuchal translucency: perinatal and two-year follow-up outcomes

This study aimed to analyze the perinatal and pediatric outcomes of fetuses with thickened nuchal translucency (NT ≥ 2.5 mm) to enhance prenatal diagnostic strategies. A total of 720 pregnant women with NT ≥ 2.5 mm in the first trimester underwent interventional prenatal diagnosis. These participants were followed up during the perinatal and pediatric periods (2 years after birth). The detection rate of fetal chromosomal karyotype abnormalities was 32.86%, with trisomy 21 being the most common abnormality. Chromosomal microarray analysis (CMA) and copy number variation sequencing (CNV-seq) increased the detection rate by 10.72%. The most prevalent pathogenic copy number variations (pCNVs) and likely pathogenic copy number variations (lpCNVs) were associated with 22q11.21 microdeletion/duplication syndrome and 15q11.2 microdeletion syndrome, respectively. Excluding pathogenic karyotype abnormalities and pCNV/lpCNVs, the rate of pathological deformities was 19.6%. Whole-exome sequencing (WES) was performed in 11 cases, yielding a detection rate of 72.7% (8/11). There were 339 pregnancy terminations and 381 live births, of which 337 had normal karyotypes, CNVs, and ultrasound results, resulting in a live-birth detection rate of 96.8%. In addition, two cases of psychomotor retardation were identified. Traditional karyotyping, CMA/CNV-seq testing, and detailed ultrasound examinations are vital diagnostic tools that support genetic counseling for fetuses with thickened NT in the first trimester. Therefore, novel and efficient WES testing is required. • Thickened NT linked to high chromosomal risk. • CMA/CNV-seq improved detection beyond karyotype. • WES showed high yield in selected cases.