BACKGROUND AND PURPOSE:

• There are differing nuchal translucency (NT) measurement thresholds for offering invasive diagnostic testing
• Sagi-Dain et al. (Obstetrics & Gynecology, 2021) examined the risk for clinically significant chromosomal microarray findings in fetuses with NT measuring 3.0 to 3.4 mm

METHODS:

• Retrospective cohort study
• Population
  • Chromosomal microarray analysis tests performed due to NT measurement from 3.0–3.4 mm
  • No fetal structural anomalies seen on ultrasound
• Study design
  • The authors compared rates of clinically significant microarray findings against a previously published local control population
    • Control population had normal ultrasound findings and NT <3.0 mm
  • Clinically significant microarray findings were defined as pathogenic and likely pathogenic copy number variants (CNVs)
  • Yield of NIPT was also assessed

RESULTS:

• 619 chromosomal microarray analyses were included
• Cases with nuchal translucency from 3.0 to 3.4 mm had significantly higher risk for significant CNVs
  • Study population: 4.7% (29 cases) with CNVs
  • Relative risk 3.3 (95% CI, 2.6 to 7.2)
  • Relationship between each millimeter increment and increased risk for significant CNV
• NIPT and/or karyotype
  • NIPT including 5 common chromosome aneuploidies could in theory have detected 17 of the abnormal cases
    • 41.4% of the abnormal CNVs would be missed | Represents 1.9% of NTs measuring 3 to 3.4 mm
  • Genome-wide NIPT or traditional karyotyping
    • Would have detected an additional 3 cases
    • Would have missed the remaining 9 cases that could only be detected with microarray

CONCLUSION:

• Isolated NT between 3.0 and 3.4mm is associated with increased risk for CNVs compared to a historic control cohort
• For fetuses with normal ultrasound and NT between 3.0 and 3.4mm
  • NIPT could miss 1.94% of fetuses with abnormal findings
  • Genome-wide NIPT or karyotype could miss 1.5% of fetuses with abnormal findings
• The authors state

Our results support 3.1 mm as the cutoff for abnormal nuchal translucency

In addition, because more than 40% of the fetuses with clinically significant chromosomal microarray analysis results would be missed by NIPT, it seems that cell-free DNA testing may not adequately replace invasive testing for chromosomal microarray analysis in such cases 

Learn More – Primary Sources:

Risk of Clinically Significant Chromosomal Microarray Analysis Findings in Fetuses With Nuchal Translucency From 3.0 mm Through 3.4 mm

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