Different Cutoff Values for Increased Nuchal Translucency in First-Trimester Screening to Predict Fetal Chromosomal Abnormalities

Abstract

Introduction: Increased nuchal translucency (NT) is closely related to an increased risk of chromosomal abnormalities. However, the criterion of increased NT for invasive prenatal diagnosis remains controversial, as the cutoff values are inconsistent among countries. This study was conducted to compare the various cutoff values of increased NT and calculate the incidence of chromosomal abnormalities to determine the predictive ability of these cutoff values in conventional chromosome analysis.

Methods: A total of 3223 invasive samples with increased nuchal translucency (NT) or other non-ultrasound indications were collected from singleton pregnant women. Samples with isolated increased NT were divided into five groups based on the NT thickness: 909 samples in the NT ≥2.5 mm group, 819 samples in the NT ≥95th group, 547 samples in the NT ≥99th group, 527 samples in the NT ≥3.0 mm group, and 253 samples in the NT ≥3.5 mm group; 2301 samples with normal NT were considered as the control group. All five groups were karyotyped and the results were compared. The accuracy of the NT cutoff value for the screening of chromosomal abnormalities was assessed using receiver operating characteristic curve analysis.

Results: Detection of all chromosomal aberrations and trisomy 21 showed that the sensitivity and false-positive rate decreased sequentially in the NT ≥2.5 mm, NT ≥95th, NT ≥3 mm, NT ≥99th, and NT ≥3.5 mm groups, whereas the specificity, positive predictive value, and false-negative rates increased sequentially. Comprehensive analysis of various factors, including sensitivity and specificity, revealed values equal to or higher than the calculated 95th percentile of NT distribution, which showed a sensitivity of 49.2% and specificity of 75.67% for detecting all aneuploidies and a sensitivity of 64% and specificity of 75.45% for trisomy 21, exhibiting the highest ability for the screening of chromosomal defects in first-trimester screening.

Conclusion: For different thresholds of NT thickness, values equal to or higher than the calculated 95th percentile of the NT distribution showed the highest ability for the screening of chromosomal defects in first-trimester screening.

Keywords: chromosomal abnormalities; crown-rump length; cutoff value; first-trimester screening; invasive prenatal diagnosis; nuchal translucency; trisomy 21.

Figure 1

Effectiveness of screening for chromosomal aberrations using different cutoff values for fetal nuchal translucency (NT). ROC curve of NT: NT ≥2.5 mm: area under the curve (AUC) = 0.619, 95% confidence interval (CI) = 0.571–0.667, P < 0.0001. NT ≥95th: AUC = 0.624, 95% CI = 0.575–0.672, P < 0.0001. NT ≥99th: AUC = 0.610, 95% CI = 0.560–0.660, P < 0.0001. NT ≥3.0 mm: AUC = 0.616, 95% CI = 0.566–0.666, P < 0.0001. NT ≥3.5 mm: AUC = 0.599, 95% CI = 0.548–0.651, P < 0.0001.

Figure 2

Effectiveness of screening for trisomy 21 using diffident cutoff values of fetal nuchal translucency (NT). ROC curve of NT: NT ≥2.5 mm: area under the curve (AUC) = 0.692, 95% confidence interval (CI) = 0.630–0.755, P < 0.0001. NT ≥95th: AUC = 0.700, 95% CI = 0.637–0.755, P < 0.0001. NT ≥ 99th: AUC = 0.682, 95% CI = 0.614–0.751, P < 0.0001. NT ≥3.0 mm: AUC = 0.679, 95% CI = 0.610–0.748, P < 0.0001. NT ≥3.5 mm: AUC = 0.642, 95% CI = 0.569–0.714, P < 0.0001.