Tags

Type your tag names separated by a space and hit enter

Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis.
Ultrasound Obstet Gynecol 2019; 53(6):734-742UO

Abstract

OBJECTIVES

To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy and to define the performance of the test by combining our results with those identified in a systematic review of the literature.

METHODS

The data for the prospective study were derived from screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation. Two populations were included; first, self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and, second, women selected for the cfDNA test after routine first-trimester combined testing at one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) 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. A meta-analysis was then performed using our data and those in the studies identified by the literature search.

RESULTS

In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 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 962 (99.4%) of the 968 cases without any of the three trisomies. The literature search identified seven relevant studies, excluding our previous papers because their data are included in the current study. In the combined populations of our study and the seven studies identified by the literature search, there were 56 trisomy-21 and 3718 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 98.2% (95% CI, 83.2-99.8%) and 0.05% (95% CI, 0.01-0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3143 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 88.9% (95% CI, 64.8-97.2%) and 0.03% (95% CI, 0.00-0.33%), respectively. For trisomy 13, there were only three affected cases and two (66.7%) of these were detected by the cfDNA test at a FPR of 0.19% (5/2569).

CONCLUSIONS

The performance of cfDNA testing for trisomy 21 in twin pregnancy is similar to that reported in singleton pregnancy and is superior to that of the first-trimester combined test or second-trimester biochemical testing. The number of cases of trisomies 18 and 13 is too small for accurate assessment of the predictive performance of the cfDNA test. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Authors+Show Affiliations

Fetal Medicine Research Institute, King's College Hospital, London, UK. Obstetrics and Gynecology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Madrid, Spain. School of Health Sciences, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain.Fetal Medicine Research Institute, King's College Hospital, London, UK. Department of Fetal Medicine, Medway Maritime Hospital, Gillingham, UK.Department of Obstetrics and Gynecology, University Hospital Brugmann, Université Libre de Bruxelles, Brussels, Belgium.Fetal Medicine Research Institute, King's College Hospital, London, UK.Department of Fetal Medicine, Medway Maritime Hospital, Gillingham, UK. Institute of Medical Sciences, Canterbury Christ Church University, Chatham, UK.Department of Preventive Medicine and Public Health, Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain. CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.Fetal Medicine Research Institute, King's College Hospital, London, UK.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31165549

Citation

Gil, M M., et al. "Screening for Trisomies By cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis." Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, vol. 53, no. 6, 2019, pp. 734-742.
Gil MM, Galeva S, Jani J, et al. Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis. Ultrasound Obstet Gynecol. 2019;53(6):734-742.
Gil, M. M., Galeva, S., Jani, J., Konstantinidou, L., Akolekar, R., Plana, M. N., & Nicolaides, K. H. (2019). Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis. Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology, 53(6), pp. 734-742. doi:10.1002/uog.20284.
Gil MM, et al. Screening for Trisomies By cfDNA Testing of Maternal Blood in Twin Pregnancy: Update of the Fetal Medicine Foundation Results and Meta-analysis. Ultrasound Obstet Gynecol. 2019;53(6):734-742. PubMed PMID: 31165549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis. AU - Gil,M M, AU - Galeva,S, AU - Jani,J, AU - Konstantinidou,L, AU - Akolekar,R, AU - Plana,M N, AU - Nicolaides,K H, Y1 - 2019/06/04/ PY - 2019/03/05/received PY - 2019/03/12/revised PY - 2019/03/14/accepted PY - 2019/6/6/pubmed PY - 2019/6/6/medline PY - 2019/6/6/entrez KW - cell-free DNA KW - first-trimester screening KW - meta-analysis KW - non-invasive prenatal testing KW - trisomy 13 KW - trisomy 18 KW - trisomy 21 KW - twin pregnancy SP - 734 EP - 742 JF - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology JO - Ultrasound Obstet Gynecol VL - 53 IS - 6 N2 - OBJECTIVES: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancy and to define the performance of the test by combining our results with those identified in a systematic review of the literature. METHODS: The data for the prospective study were derived from screening for trisomies 21, 18 and 13 in twin pregnancies at 10 + 0 to 14 + 1 weeks' gestation. Two populations were included; first, self-referred women to the Fetal Medicine Centre in London or Brugmann University Hospital in Brussels and, second, women selected for the cfDNA test after routine first-trimester combined testing at one of two National Health Service hospitals in England. This dataset was used to determine the performance of screening for the three trisomies. Search of MEDLINE, EMBASE, CENTRAL (The Cochrane Library), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) 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. A meta-analysis was then performed using our data and those in the studies identified by the literature search. RESULTS: In our dataset of 997 twin pregnancies with a cfDNA result and known outcome, the test classified correctly 16 (94.1%) of the 17 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 962 (99.4%) of the 968 cases without any of the three trisomies. The literature search identified seven relevant studies, excluding our previous papers because their data are included in the current study. In the combined populations of our study and the seven studies identified by the literature search, there were 56 trisomy-21 and 3718 non-trisomy-21 twin pregnancies; the pooled weighted detection rate (DR) and false-positive rate (FPR) were 98.2% (95% CI, 83.2-99.8%) and 0.05% (95% CI, 0.01-0.26%), respectively. In the combined total of 18 cases of trisomy 18 and 3143 non-trisomy-18 pregnancies, the pooled weighted DR and FPR were 88.9% (95% CI, 64.8-97.2%) and 0.03% (95% CI, 0.00-0.33%), respectively. For trisomy 13, there were only three affected cases and two (66.7%) of these were detected by the cfDNA test at a FPR of 0.19% (5/2569). CONCLUSIONS: The performance of cfDNA testing for trisomy 21 in twin pregnancy is similar to that reported in singleton pregnancy and is superior to that of the first-trimester combined test or second-trimester biochemical testing. The number of cases of trisomies 18 and 13 is too small for accurate assessment of the predictive performance of the cfDNA test. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. SN - 1469-0705 UR - https://www.unboundmedicine.com/medline/citation/31165549/Screening_for_trisomies_by_cfDNA_testing_of_maternal_blood_in_twin_pregnancy:_update_of_The_Fetal_Medicine_Foundation_results_and_meta_analysis_ L2 - https://doi.org/10.1002/uog.20284 DB - PRIME DP - Unbound Medicine ER -