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

Journal article


Judah, H., Gil, M., Syngelaki, A., Galeva, S., Jani, J., Akolekar, R. and Nicolaides, K. H. 2021. Cell‐free <scp>DNA</scp> testing of maternal blood in screening for trisomies in twin pregnancy: updated cohort study at 10–14 weeks and meta‐analysis. Ultrasound in Obstetrics & Gynecology. 58 (2), pp. 178-189. https://doi.org/10.1002/uog.23648
AuthorsJudah, H., Gil, M., Syngelaki, A., Galeva, S., Jani, J., Akolekar, R. and Nicolaides, K. H.
AbstractABSTRACTObjectiveTo 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.MethodsThe 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), 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 reviewsResultsIn 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.ConclusionsIn 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 cases of trisomy 18 and more so trisomy 13 was too small for accurate assessment of the predictive performance of the cfDNA test. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
KeywordsObstetrics and Gynecology; Radiology, Nuclear Medicine and imaging; Reproductive Medicine; General Medicine; Radiological and Ultrasound Technology
Year2021
JournalUltrasound in Obstetrics & Gynecology
Journal citation58 (2), pp. 178-189
PublisherWiley
ISSN0960-7692
1469-0705
Digital Object Identifier (DOI)https://doi.org/10.1002/uog.23648
Official URLhttps://obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.23648
Publication dates
Online10 Jul 2021
Publication process dates
Deposited16 Aug 2021
Accepted02 Apr 2021
Output statusPublished
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Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates
Ciobanu, A., Khan, N., Syngelaki, A., Akolekar, R. and Nicolaides, K. H. 2019. Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates. Ultrasound in Obstetrics and Gynecology. 53 (6), pp. 761-768. https://doi.org/10.1002/uog.20258
Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks
Ciobanu, A., Anthoulakis, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (5), pp. 630-637. https://doi.org/10.1002/uog.20267
Maternal and neonatal complications of fetal macrosomia: cohort study
Beta, J., Khan, N., Fiolna, M., Khalil, A., Ramadan, G. and Akolekar, R. 2019. Maternal and neonatal complications of fetal macrosomia: cohort study. Ultrasound in Obstetrics and Gynecology. 54 (3), pp. 319-325. https://doi.org/10.1002/uog.20279
Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis
Beta, J., Zhang, W., Geris, S., Kostiv, V. and Akolekar, R. 2019. Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 452-457. https://doi.org/10.1002/uog.20293
Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Ciobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H. 2019. Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 54 (1), pp. 79-86. https://doi.org/10.1002/uog.20346
Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis
Salomon, L. J., Sotiriadis, A., Wulff, C. B., Odibo, A. and Akolekar, R. 2019. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 442-451. https://doi.org/10.1002/uog.20353
Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound
Khan, N., Ciobanu, A., Karampitsakos, T., Akolekar, R. and Nicolaides, K. H. 2019. Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound. Ultrasound in Obstetrics and Gynecology. 54 (2), pp. 326-333. https://doi.org/10.1002/uog.20377
Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation
Akolekar, R., Panaitescu, A. M., Ciobanu, A., Syngelaki, A. and Nicolaides, K. H. 2019. Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 54, pp. 484-491. https://doi.org/10.1002/uog.20391
Prevention of stillbirths: impact of a two-stage screening for vasa previa
Zhang, W., Geris, S., Beta, J., Ramadan, G., Nicolaides, K. H. and Akolekar, R. 2019. Prevention of stillbirths: impact of a two-stage screening for vasa previa. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 605-612. https://doi.org/10.1002/uog.21953
Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta
Vigneswaran, T. V., Zidere, V., Chivers, S., Charakida, M., Akolekar, R. and Simpson, J. M. 2019. Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.21957
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus
Minnella, G. P., Crupano, F. M., Syngelaki, A., Zidere, V., Akolekar, R. and Nicolaides, K. H. 2019. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 637-644. https://doi.org/10.1002/uog.21956
Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation
Dragan, I., Georgiou, T., Prodan, N., Akolekar, R. and Nicolaides, K. H. 2017. Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (1), pp. 73-77. https://doi.org/10.1002/uog.17301
Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (3), pp. 308-315. https://doi.org/10.1002/uog.14898
Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 194-202. https://doi.org/10.1002/uog.14928
Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result
Revello, R., Sarno, L., Ispas, A., Akolekar, R. and Nicolaides, K. H. 2016. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 698-704. https://doi.org/10.1002/uog.15851
Metformin versus placebo in obese pregnant women without diabetes mellitus
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., Pastides, A. and Shehata, H. 2016. Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine. 374, pp. 434-43. https://doi.org/10.1056/NEJMoa1509819
Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy
Sarno, L., Revello, R., Hanson, E., Akolekar, R. and Nicolaides, K. H. 2016. Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 705-11. https://doi.org/10.1002/uog.15913
Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks
Mastrodima, S., Akolekar, R., Yerlikaya, G., Tzelepis, T. and Nicolaides, K. H. 2016. Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 613-617. https://doi.org/10.1002/uog.17289
Prediction of stillbirth from maternal demographic and pregnancy characteristics
Yerlikaya, G., Akolekar, R., McPherson, K., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal demographic and pregnancy characteristics. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 607-612. https://doi.org/10.1002/uog.17290
Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies
Peeva, G., Chaveeva, P., Gil Guevara, E., Akolekar, R. and Nicolaides, K. H. 2016. Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies. Fetal Diagnosis and Therapy. 40 (3), pp. 174-180. https://doi.org/10.1159/000443792
Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks
Akolekar, R., Tokunaka, M., Ortega, N., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 624-630. https://doi.org/10.1002/uog.17295
Prediction of stillbirth from placental growth factor at 11-13 weeks
Akolekar, R., Machuca, M., Mendes, M., Paschos, V. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 618-623. https://doi.org/10.1002/uog.17288
Prediction of stillbirth from placental growth factor at 19-24 weeks
Aupont J. E., Akolekar, R., Illian, A., Neonakis, S. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 631-635. https://doi.org/10.1002/uog.17229
Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2015. Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 203-209. https://doi.org/10.1002/uog.15663