Routine First-Trimester Screening for Fetal Trisomies in Twin Pregnancy: Cell-free DNA Test Contingent on Results From Combined Test

Galeva, S.; Konstantinidou, L.; Gil, M. M.; Akolekar, Ranjit; Nicolaïdes, K. H.

doi:10.1097/01.ogx.0000569248.49687.19

Cited by 7 publications

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“…The literature search identified 381 potentially relevant citations, but 366 were excluded because they were not relevant, a conference abstract rather than a peer‐reviewed paper, a review article, an opinion, not confined to twins, a case–control study, a study on clinical implementation of cfDNA testing in screening for aneuploidy in which pregnancy outcome data were provided for fewer than 85% of the study population or a proof‐of‐principle study reporting laboratory techniques rather than clinical validation of a predefined method of maternal blood cfDNA analysis (Figure 2). In total, 15 relevant studies were identified 2,13–26 but three of these 2,13,14 were excluded from the meta‐analysis because their data are included in the updated FMF results presented above. The characteristics of our current study and the 12 studies identified by the literature search are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…The literature search identified 12 studies reporting on screening for trisomy in twin pregnancies by cfDNA testing of maternal blood, in addition to our previous studies, the data from which are included in the current FMF study. The main features of these 12 studies are, first, the method of cfDNA testing was by MPSS in 11 studies and by targeted testing in only one, second, none of the studies was confined to the first trimester and, in some cases, testing was carried out as late as 36 weeks' gestation 16,26 , and, third, in nine of the studies, the cfDNA test provided a result in > 99% of cases 15–18,20,22,23,25,26 and, in six of the studies, pregnancy outcome was apparently obtained in > 99% of cases 14,16,18,21,23,24 .…”

Section: Discussionmentioning

confidence: 99%

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Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

Judah

Gil

Syngelaki

et al. 2021

Ultrasound in Obstet & Gyne

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Objective To expand the limited knowledge on cell‐free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy by updating the data from The Fetal Medicine Foundation (FMF) on prospective first‐trimester screening and those identified in a systematic review of the literature. Methods The FMF data were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation using the Harmony® prenatal test. A search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), http://ClinicalTrials.gov and the International Clinical Trials Registry Platform (World Health Organization) was carried out to identify all peer‐reviewed publications on clinical validation or implementation of maternal cfDNA testing for trisomies 21, 18 and 13 in twin pregnancy, irrespective of gestational age at testing, in which data on pregnancy outcome were provided for at least 85% of the study population. Meta‐analysis was performed using the FMF data and data from the studies identified by the literature search. This review was registered in the PROSPERO international database for systematic reviews Results In the FMF study, cfDNA testing was carried out in 1442 twin pregnancies and a result was obtained, after first or second sampling, in 1367 (94.8%) cases. In 93.1% (1272/1367) of cases, there was prenatal or postnatal karyotyping or birth of phenotypically normal babies; 95 cases were excluded from further analysis either because the pregnancy ended in termination, miscarriage or stillbirth with no known karyotype (n = 56) or there was loss to follow‐up (n = 39). In the 1272 pregnancies included in the study, there were 20 cases with trisomy 21, 10 with trisomy 18, two with trisomy 13 and 1240 without trisomy 21, 18 or 13. The cfDNA test classified correctly 19 (95.0%) of the 20 cases of trisomy 21, nine (90.0%) of the 10 cases of trisomy 18, one (50.0%) of the two cases of trisomy 13 and 1235 (99.6%) of the 1240 cases without any of the three trisomies. The literature search identified 12 relevant studies, excluding our papers because their data are included in the current study. In the combined populations of our study and the 12 studies identified by the literature search, there were 137 trisomy‐21 and 7507 non‐trisomy‐21 twin pregnancies; the pooled weighted detection rate (DR) and false‐positive rate (FPR) were 99.0% (95% CI, 92.0–99.9%) and 0.02% (95% CI, 0.001–0.43%), respectively. In the combined total of 50 cases of trisomy 18 and 6840 non‐trisomy‐18 pregnancies, the pooled weighted DR and FPR were 92.8% (95% CI, 77.6–98.0%) and 0.01% (95% CI, 0.00–0.44%), respectively. In the combined total of 11 cases of trisomy 13 and 6290 non‐trisomy‐13 pregnancies, the pooled weighted DR and FPR were 94.7% (95% CI, 9.14–99.97%) and 0.10% (95% CI, 0.03–0.39%), respectively. Conclusions In twin pregnancy, the reported DR of trisomy 21 by cfDNA testing is high, but lower than that in singleton pregnancy, whereas the FPR appears to be equally low. The number of...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

Judah

Gil

Syngelaki

et al. 2021

Ultrasound in Obstet & Gyne

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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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“…55,58 Any one or more of the fetal fraction measurement methods have been used in combination with whole-genome or targeted cfDNA aneuploidy screening tests (Table 3). 69 While some programs use a fixed fetal fraction cut-off to determine adequacy, other methods are also utilized. In multifetal pregnancies, this cut-off is dependent on whether total fetal fraction or individual fetal fraction is measured and whether the twins are likely monozygous or likely dizygous.…”

Section: Fetal Fraction Measurements Among Multiple Pregnanciesmentioning

confidence: 99%

International Society for Prenatal Diagnosis Position Statement: cell free (cf)DNA screening for Down syndrome in multiple pregnancies

et al. 2020

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Routine First-Trimester Screening for Fetal Trisomies in Twin Pregnancy: Cell-free DNA Test Contingent on Results From Combined Test

Cited by 7 publications

References 0 publications

Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

Cell‐free DNA testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis

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

International Society for Prenatal Diagnosis Position Statement: cell free (cf)DNA screening for Down syndrome in multiple pregnancies

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