Chromosomal and genetic anomalies in fetuses with nuchal translucency between 3.0 and 3.4 mm: A systematic review and...

To report the prevalence of chromosomal anomalies in fetuses with a nuchal translucency (NT) between 3.0 and 3.4 mm and to assess the incremental yield of invasive prenatal diagnosis over cell-free DNA (cfDNA) in these fetuses.

MEDLINE, EMBASE, and The Cochrane Library were searched. Inclusion criteria encompassed fetuses with an NT between 3.0 and 3.4 mm undergoing prenatal invasive testing or postnatal genetic assessment. The observed outcomes included common trisomies such as Trisomy 21, 18, and 13, sex chromosomal anomalies (SCAs), rare autosomal anomalies, copy number variants detected by chromosomal microarray (CMA), and single-gene disorders. We also reported the rate of anomalies potentially detectable by cfDNA. Finally, we planned to perform a subgroup analysis involving cases with isolated NT between 3.0 and 3.4 mm, including only cases undergoing detailed first-trimester ultrasound assessment. A random-effects meta-analysis of proportions was utilized to analyze the data.

Seventeen studies (7007 fetuses) were included. In fetuses with NT measurements between 3.0 and 3.4 mm, chromosomal anomalies were identified in 13.1% (95% CI 9.3-17.3). Common trisomies included Trisomy 21 at 8.0% (95% CI 5.1-11.5), Trisomy 18 at 1.0% (95% CI 0.6-1.7), and Trisomy 13 at 0.52% (95% CI 0.2-1.0) of all chromosomal anomalies. SCAs occurred in 0.58% (95% CI 0.4-0.8), while rare autosomal trisomies and pathogenic or likely pathogenic copy number variants (CNVs) were found in 0.27% (95% CI 0.1-0.6) and 2.5% (95% CI 1.3-3.9), respectively. Additionally, single-gene disorders detected via NGS/WES were reported in 5.7% (95% CI 3.3-8) of cases with NT between 3.0 and 3.4 mm. When examining only fetuses with an isolated NT between 3.0 and 3.4 mm, all chromosomal anomalies were identified in 12.4% (95% CI 7.9-17.7).

Fetuses with an NT between 3.0 and 3.4 mm showed a high rate of chromosomal anomalies and CNVs, most of which could potentially be detected through cfDNA.