Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result

Journal article


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
AuthorsRevello, R., Sarno, L., Ispas, A., Akolekar, R. and Nicolaides, K. H.
Abstract

Objectives:
First, to report the distribution of fetal fraction and the rate of failed result in trisomies
21, 18 and 13 , by comparison with pregnancies unaffected by these trisomies, secondly, examine the possible effects of maternal and fetal characteristics on the fetal fraction and thirdly, consider the options for the further management of pregnancies with failed cfDNA result.

Methods:
This was a cohort study of 10,698 singleton pregnancies undergoing screening for fetal trisomies 21, 18 and 13 by cfDNA testing at 10 14 weeks’ gestation There were 160 cases of trisomy 21, 50 of trisomy 18, 16 of trisomy 13 and 10,472 unaffected by these trisomies. Multivariate regression analysis was used to determine significant predictors of fetal fraction and failed result amongst maternal and fetal characteristics.

Results:
Fetal fraction decreased with increasing body m ass index and maternal age, was lower in women of South Asian racial origin than in Caucasians and in assisted than natural conceptions, and increased with fetal crown rump length, serum PAPP A and free  hCG. The median fetal fraction was 11.0% (IQR 8.3-14.4%) in the unaffected group, 10.7% (IQR 7.8-14.3%) in trisomy 21, 8.6% (IQR 5.0-10.2%) in trisomy 18 and 7.0% (IQR 6.0-9.4%) in trisomy 13. There was a failed result from cfDNA testing after first sampling in 2.9% of the unaffected group, 1.9% of trisomy 21, 8.0% of trisomy 18 and 6.3% of trisomy 13. In the cases of failed result, 7% of women had invasive testing, mainly because of high risk from the combined test and/or presence of sonographic features suggestive of trisomies 18 and 13. All cases of trisomies were detected prenatally.

Conclusions:
In cases of failed cfDNA test the rate of trisomies 18 and 13, but not trisomy 21, are higher than in those with a successful test. In the management of such cases, the decision in favor of invasive testing sh ould depend on the risk of prior screening and the results of detailed ultrasound examination.

KeywordsCell free DNA; First trimester Screening; Trisomy 21; Fetal fraction; Non invasive prenatal testing
Year2016
JournalUltrasound in Obstetrics and Gynecology
Journal citation47 (6), pp. 698-704
PublisherWiley
ISSN0960-7692
Digital Object Identifier (DOI)https://doi.org/10.1002/uog.15851
Official URLhttps://doi.org/10.1002/uog.15851
FunderFetal Medicine Foundation
Publication dates
Online25 Apr 2016
Publication process dates
Accepted31 Dec 2015
Deposited11 May 2020
Accepted author manuscript
Output statusPublished
Additional information

Fetal Medicine Foundation Grant Number: 1037116

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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
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