Abstract
Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). On top of that, these limited number of researches were all designed as single-arm studies and the control group was missing. In this study, we conducted a multicenter, retrospective study using amniotic fluid samples collected from 1197 pregnant women having fetuses with isolated increased NT (INT group) or normal NT values (NNT group). Copy number variation sequencing (CNV-seq) was performed to determine their chromosome status and pathogenic variations were validated using SNP array. Overall, 59 chromosome aneuploidies, 34 pathogenic CNVs and 23 copy number variants of unknown significance (VOUS CNVs) were discovered. the INT group had a significantly higher proportion of aneuploidy (19.44%) and pathogenic CNV (8.33%) than the control group (3.49% and 2.30% respectively), and 88.89% of the pathogenic CNVs were related to heart defects. Additionally, more male fetuses were presented in the INT group (68.51%), but they did not have a higher risk (Relative Risk = 1.03) of carrying pathogenic chromosome variations than female fetuses. Our results demonstrated that fetuses with isolated increased NT had a distinct pattern of chromosome abnormality and majority of detected pathogenic CNVs could be linked to the congenital heart disease. Furthermore, because a considerable proportion of pathogenic CNVs were detected, we strongly recommend to perform a joint test of karyotyping and CNV analysis in prenatal diagnosis for fetuses with isolated increased NT in order to decrease the incident of missed diagnosis.
Highlights
Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT)
Previous publications demonstrated that on top of the increased incidents of chromosome aneuploidies. various percentages of pathogenic copy number variation (CNV) ranging from 0% to 12.8%11–13 and high prevalence of congenital heart defects (CHD) and neurodevelopmental disorders were could be found in fetuses with isolated increased NT14
Our results showed that 8.33% of the fetuses in the isolated increased NT group carried pathogenic CNVs (pCNVs), which was significantly different (P < 0.001, relative risk = 3.62) than those in the normal NT group
Summary
Extensive researches involving fetuses with multiple ultrasound anomalies have been conducted over the years, but only few were focused on the isolated increased nuchal translucency (NT). Various percentages of pathogenic CNVs ranging from 0% to 12.8%11–13 and high prevalence of congenital heart defects (CHD) and neurodevelopmental disorders were could be found in fetuses with isolated increased NT14. These researches were all designed as a single-arm study, and without a proper control group, results can only be compared with external historical data of other related work, which made it difficult to diminish the effects caused by different enrollment criteria among studies.
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