BACKGROUND AND PURPOSE:

• Guidelines (e.g., ACOG/SMFM) recommend that a nuchal translucency (NT) ≥3.0 mm be used to offer genetic testing even if a noninvasive screen in negative
• Hui et al. (AJOG, 2021) determined the optimal definition of an enlarged NT for the detection of atypical chromosome abnormalities

METHODS:

• Retrospective population-based study
  • Data over a 2-year period (January 2015 to December 2016)
• Population
  • Women in Victoria, Australia undergoing combined first trimester screening
• Study design
  • Individual linked data
    • Combined first-trimester screening results
    • Prenatal diagnostic procedures
    • Postnatal cytogenetic results: From POC and infants up to 12 months of age
• Primary outcome
  • Atypical chromosome abnormality: Any major chromosome abnormality other than whole chromosome aneuploidy involving chromosomes 21, 18, 13, X, and Y

RESULTS:

• 81,244 singleton pregnancies undergoing first-trimester screening
  • NT measurements
    • ≥3.5 mm: 0.60%
    • 3.0 to 3.4 mm: 0.66%
    • <3.0 mm: 98.74%
  • NT multiples of the median (MoM) adjusted for gestational age
    • ≥3.0 MoM: 0.24%
    • 1.9 to 2.9 MoM: 0.63%
    • 1.9 MoM: 99.13%
• 1779 pregnancies underwent prenatal or postnatal diagnostic testing
  • Whole-genome single-nucleotide polymorphism chromosomal microarray: 89.60%
  • Atypical chromosome abnormalities found: 93 total
• The frequency of total major chromosome abnormalities was significantly higher in the group with a NT of ≥3.5 mm (P<0.001)
  • ≥3.5 mm: 29.94%
  • 3.0 to 3.4 mm: 3.93%
  • <3.0 mm: 0.09%
• Frequencies of atypical chromosome abnormality by
  • NT measurement
    • ≥3.5 mm: 4.07% (95% CI, 2.51 to 6.22)
    • 3.0 to 3.4 mm: 0.37% (95% CI, 0.05 to 1.35)
    • <3.0 mm: 0.09% (95% CI, 0.07 to 0.11)
  • NT multiples of the median (MoM)
    • ≥3.0 MoM: 4.69% (95% CI, 2.17 to 8.71)
    • 1.9 to 2.9 MoM: 2.53% (95% CI, 1.36 to 4.29)
    • 1.9 MoM: 0.09% (95% CI, 0.07 to 0.11)
• Both NT threshold of 1.9 MoM and fixed threshold of 3.0 mm captured 23.7% of fetuses with atypical chromosome abnormality
• Positive predictive value was higher using MoM
  • NT ≥3.0 mm: 1 in 47
  • NT>1.9 MoM: 1 in 32
• Impact of abnormal ultrasound
  • Isolated enlarged NT
    • NT of ≥3.0 mm: 3.07%
    • NT of ≥1.9 MoM: 3.61%
  • Additional structural anomaly
    • NT of ≥3.0 mm: 11.00%
    • NT of ≥1.9 MoM: 11.70%

CONCLUSION:

• An NT threshold of 1.9 MoM adjusted for gestational age vs a cutoff of 3.0 mm was superior for identifying other chromosome abnormalities beyond the common aneuploidies   
• The risk of an atypical chromosome abnormality in a fetus with an enlarged nuchal translucency triples with an additional ultrasound abnormality

Learn More – Primary Sources:

Reexamining the optimal nuchal translucency cutoff for diagnostic testing in the cell-free DNA and microarray era: results from the Victorian Perinatal Record Linkage study

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