Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test

Journal article


Galeva, S., Konstantinidou, L., Gil, M.M., Akolekar, R. and Nicolaides, K.H. 2019. Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test. Ultrasound in Obstetrics and Gynecology. 53 (2), pp. 208-213. https://doi.org/10.1002/uog.20160
AuthorsGaleva, S., Konstantinidou, L., Gil, M.M., Akolekar, R. and Nicolaides, K.H.
Abstract

Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 contingent on the results of the first-trimester combined test in twin pregnancies.

Methods: Screening for trisomies 21, 18 and 13 was carried out by a combination of maternal age, fetal nuchal translucency (NT) thickness, and serum free ß-hCG and PAPP-A at 11-13 weeks’ gestation in 959 twin pregnancies in two UK NHS hospitals. Women in the high-risk group (risk >1 in 100) were offered options of invasive testing, cfDNA testing or no further testing and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.

Results: In 42 (4.4%) of the 959 pregnancies there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow up. The 917 pregnancies with known trisomic status of both twins, included 6 that were discordant for trisomy 21, 4 discordant for trisomy 18 and 896 with no trisomies 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.2%) and 667 (72.7%) of the pregnancies were classified as high-risk, intermediate-risk and low-risk, respectively. The high-risk group included 5 (83.3%) cases of trisomy 21 and 3 (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included 6 with trisomy 21, 3 with trisomy 18 and 206 with no trisomies 21, 18 or 13. The cfDNA test correctly classified as screen positive all 6 cases of trisomy 21 and 2 of the 3 with trisomy 18 and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening, led to prenatal detection of all cases of trisomy 21 and 3 of 4 with trisomy 18.

Conclusions: The study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies.

KeywordsCell-free DNA; First-trimester screening; Combined test; Non-invasive prenatal testing; Trisomy 21; Trisomy 18; Trisomy 13; Twin pregnancy
Year2019
JournalUltrasound in Obstetrics and Gynecology
Journal citation53 (2), pp. 208-213
PublisherWiley
ISSN1469-0705
Digital Object Identifier (DOI)https://doi.org/10.1002/uog.20160
Official URLhttp://doi.org/10.1002/uog.20160
Publication dates
Online07 Dec 2018
Publication process dates
Accepted16 Oct 2018
Deposited03 Jun 2020
Accepted author manuscript
Output statusPublished
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