First‐trimester screening for trisomy 21 via an individualized nomogram

OBJECTIVES: To develop and validate a nomogram based on fetal nuchal translucency (NT) and ultrasonographic facial markers for the screening of trisomy 21 in the first-trimester of pregnancy. METHODS: This was a retrospective case-control study using stored 2D midsagittal fetal profile images captured at 11+0 to 13+6 weeks' gestation. Our database was used to identify 302 cases of trisomy 21 pregnancies and 322 euploid pregnancies. For each case, the maternal age and ultrasonographic facial markers were investigated. Least absolute shrinkage and selection operator (LASSO) method and multivariable analysis were used to select the discriminative markers automatically. Logistic regression was used to develop a model (LASSO-model) based on the selected markers to screen for trisomy 21 in the first-trimester of pregnancy. Furthermore, 60 cases were randomly selected as a retest set to evaluate the model's robustness. The predictive performance of the model of fetal NT and maternal age, the model of all markers of this study and the LASSO-model for the screening of trisomy 21 was assessed using area under receiver operating characteristic (ROC) curve (AUC). A nomogram was developed as an individualized tool to predict patient-specific probability for trisomy 21, which is a more intuitive presentation of the LASSO-model. The performance of the nomogram was assessed using C-index and calibration curve. RESULTS: Eight markers were incorporated into the LASSO-model, including fetal NT, prenasal thickness-to-nasal bone length ratio, facial profile line, frontomaxillary facial angle, frontonasal facial angle, mandibulomaxillary facial angle, maxilla-nasion-mandible angle, and d2 (distance between the anterior edge of the prefrontal skin and the mandibulomaxillary line) (all P-values <0.05). The AUCs of the LASSO-model for the screening of trisomy 21 were 0.983 (95% CI: 0.971-0.994) and 0.979 (95% CI: 0.966-0.993) in the training and the validation sets, respectively, which were higher than the AUCs of all eight individual ultrasonographic markers included in the LASSO-model. The AUC of the LASSO-model in the retest set was 0.997 (95% CI: 0.990-1.000), which showed the good robustness of LASSO-model. The AUC of the LASSO-model was significantly higher than the AUC of the model based on fetal NT and maternal age in both the training and the validation sets. The nomogram of LASSO-model showed a good discrimination of trisomy 21 with C-indexes of 0.983 in the training set and 0.981 in the validation set. CONCLUSION: This study has presented an individualized nomogram, which incorporates the fetal NT and a series of ultrasonographic facial profile markers selected by the LASSO-method and multivariable analysis. It can potentially be utilized as a convenient and effective tool for the screening of trisomy 21 in the first-trimester of pregnancy. This article is protected by copyright. All rights reserved.