False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell-Free DNA versus First-Trimester Combined Screening with Additional Ultrasound Markers

Kagan, Karl Oliver; Maier, Vanessa; Sonek, Jiri; Abele, Harald; Lüthgens, Kai; Schmid, Maximilian; Wagner, Philipp; Hoopmann, Markus

doi:10.1159/000489121

Cited by 12 publications

(10 citation statements)

References 24 publications

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“…For over a decade, the first-trimester combined test, including maternal age, fetal NT and maternal serum biochemistry, with a detection rate of 90% at a FPR of 5%, has played a major role in screening for trisomy 21 in the first trimester of pregnancy. In recent years, cell-free (cf)DNA testing has improved significantly the performance of screening for trisomy 21, with a detection rate of > 99% at a FPR of < 0.1% [21][22][23][24] . However, the cost of cfDNA testing is high, making it impossible to offer it to all pregnant women.…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Application of an individualized nomogram in first‐trimester screening for trisomy 21

Sun

Zhang

Dong

et al. 2021

Ultrasound in Obstet & Gyne

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Objectives To develop and validate a nomogram based on fetal nuchal translucency thickness (NT) and ultrasonographic facial markers for screening for trisomy 21 in the first trimester of pregnancy. Methods This was a retrospective case–control study using stored two‐dimensional midsagittal fetal profile images captured at 11 + 0 to 13 + 6 weeks' gestation in singleton pregnancies. We included images from 302 trisomy‐21 pregnancies and 322 euploid pregnancies. Cases were divided into a training set (200 euploid + 200 with trisomy 21) and a validation set (122 euploid + 102 with trisomy 21) at a ratio of approximately 2:1. For each, the maternal age, gestational age, fetal NT and karyotype were noted, and 12 ultrasonographic fetal facial markers were measured. The least absolute shrinkage and selection operator (LASSO) method and multivariable analysis were used to select automatically the discriminative markers. Logistic regression was used to develop a LASSO model, based on the selected markers, to screen for trisomy 21 in the first trimester of pregnancy. Furthermore, 60 of the 624 images were selected randomly as a retest set to evaluate the model's robustness. The predictive performance of screening for trisomy 21 of a model based on fetal NT and maternal age and of the LASSO model was assessed using the area under the receiver‐operating‐characteristics curve (AUC). A nomogram was developed as an individualized tool to predict patient‐specific probability for trisomy 21, which is a more visual presentation of the LASSO model. The performance of the nomogram was assessed using the C‐index and calibration curve. Results Into the LASSO model were incorporated eight markers, 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 < 0.05). The AUCs of the LASSO model for screening for trisomy 21 were 0.983 (95% CI, 0.971–0.994) in the training set and 0.979 (95% CI, 0.966–0.993) in the validation set, and these were higher than the AUCs of all eight individual ultrasonographic markers included in the model. The AUC of the LASSO model in the retest set was 0.997 (95% CI, 0.990–1.000), indicating good robustness of the LASSO model. The AUC of the LASSO model was significantly higher than that of the model based on fetal NT and maternal age in both training and validation sets (P < 0.001 for both). The nomogram of the LASSO model showed good discrimination of trisomy 21, with C‐indices of 0.983 in the training set and 0.981 in the validation set. Conclusions We present an individualized nomogram which incorporates fetal NT and a series of ultrasonographic facial profile markers selected by the LASSO method and multivariable analysis. This nomogram can potentially be utilized as a convenient and effective tool in screening for trisomy 21 in the first trimest...

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Section: Implications For Clinical Practicementioning

confidence: 99%

Application of an individualized nomogram in first‐trimester screening for trisomy 21

Sun

Zhang

Dong

et al. 2021

Ultrasound in Obstet & Gyne

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“…3,4 However, some studies have suggested that further cost-saving approaches should be explored, considering the potentially high cost of cell-free fetal DNA testing. 4,5 For decades, ultrasonographic images have been widely used for screening fetuses for trisomy 21, owing to the advantages of safety, convenience, and low cost. 6,7 Fetal nuchal translucency (NT) thickness, measured in ultrasonographic images, has been used to screen fetuses with trisomy 21.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, analyses of cell-free fetal DNA validation show high accuracy (up to 99%) in screening for trisomy 21 . However, some studies have suggested that further cost-saving approaches should be explored, considering the potentially high cost of cell-free fetal DNA testing …”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Deep Learning Model to Screen for Trisomy 21 During the First Trimester From Nuchal Ultrasonographic Images

et al. 2022

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IMPORTANCEAccurate screening of trisomy 21 in the first trimester can provide an early opportunity for decision-making regarding reproductive choices. OBJECTIVE To develop and validate a deep learning model for screening fetuses with trisomy 21 based on ultrasonographic images. DESIGN, SETTING, AND PARTICIPANTS This diagnostic study used data from all available cases and controls enrolled at 2 hospitals in China between January 2009 and September 2020. Two-dimensional images of the midsagittal plane of the fetal face in singleton pregnancies with gestational age more than 11 weeks and less than 14 weeks were examined. Observers were blinded to subjective fetus nuchal translucency (NT) marker measurements. A convolutional neural network was developed to construct a deep learning model. Data augmentation was applied to generate more data. Different groups were randomly selected as training and validation sets to assess the robustness of the deep learning model. The fetal NT was shown and measured. Each detection of trisomy 21 was confirmed by chorionic villus sampling or amniocentesis. Data were analyzed from

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“…Women in their first 3 months of pregnancy are offered first trimester combined screening (FTCS), based on maternal age, fetal nuchal translucency thickness (NT) and serum markers such as beta human chorionic gonadotropin (β-HCG) and pregnancy-associated plasma protein A (PAPP-A), with a detection rate for T21 of 90–95% and a false positive rate of 2.5–5% ( Kagan et al, 2019 ), as well as a positive predicted value of 3.4% ( Norton et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Two cases of apparent discordance between non-invasive prenatal testing (NIPT) and amniocentesis resulting in feto-placental mosaicism of trisomy 21. Issues in diagnosis, investigation and counselling

Feresin

Stampalija²,

Cappellani³

et al. 2022

Front. Genet.

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The sequencing of cell-free fetal DNA in the maternal plasma through non-invasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and feto-placental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms.

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False-Positive Rate in First-Trimester Screening Based on Ultrasound and Cell-Free DNA versus First-Trimester Combined Screening with Additional Ultrasound Markers

Cited by 12 publications

References 24 publications

Application of an individualized nomogram in first‐trimester screening for trisomy 21

Application of an individualized nomogram in first‐trimester screening for trisomy 21

Development and Validation of a Deep Learning Model to Screen for Trisomy 21 During the First Trimester From Nuchal Ultrasonographic Images

Case Report: Two cases of apparent discordance between non-invasive prenatal testing (NIPT) and amniocentesis resulting in feto-placental mosaicism of trisomy 21. Issues in diagnosis, investigation and counselling

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