Browsing by Author "Konstantinidou, Liountmila"
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Item First-trimester screening for trisomies by cfDNA testing of maternal blood in singleton and twin pregnancies: factors affecting test failure.(Ultrasound in Obstetrics and Gynecology, 2019) Galeva, Slavyana; Gil Mira, María del Mar; Konstantinidou, Liountmila; Akolekar, Ranjit; Nicolaides, Kypros H.Objectives: To examine factors affecting the failure rate to obtain a result from (cf) DNA testing of maternal blood for fetal trisomies 21, 18 and 13 in singleton and twin pregnancies in the first trimester of pregnancy. Methods: This was a prospective study in 23,495 singleton and 928 twin pregnancies undergoing screening for fetal trisomies by targeted cfDNA testing at 10+0-14+1 weeks’ gestation. Multivariate regression analysis was used to determine significant predictors of failure to obtain a result after first sampling. Results: There was no result from cfDNA testing after first sampling in 3.4% (798/23,495) of singletons, 11.3% (91/806) of DC twins and in 4.9% (6/122) of MC twins. Multivariate logistic regression analysis demonstrated that the risk of test failure first, increased with increasing maternal age (odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01, 1.04) and weight (OR 1.05; 95% CI 1.04, 1.05), decreasing gestational age (OR 0.85; 95% CI 0.79, 0.91) and serum PAPP-A (OR 0.56; 95% CI 0.49, 0.64) and free ß-hCG (OR 0.67; 95% CI 0.60, 0.74), second, was higher in women of Black (OR 1.72; 95% CI 1.33, 2.20) and South Asian (OR 1.99; 95% CI 1.56, 2.52) than White racial origin, in dichorionic twin (OR 1.75; 95% CI 1.34, 2.25) than singleton pregnancy and in in vitro fertilization (OR 3.82; 95% CI 3.19, 4.55) than natural conception and third, was lower in parous (OR 0.63; 95% CI 0.55, 0.74) than nulliparous women. Conclusions: Maternal age, weight, racial origin and parity, gestational age, dichorionicity, method of conception and serum levels of free ß-hCG and PAPP-A are independent predictors of cfDNA test failure. The risk of test failure is higher in dichorionic twin than in singleton pregnancies, mainly because a higher proportion of twins are conceived by in vitro fertilization and more of the women are nulliparous.Item Routine first-trimester screening for fetal trisomies in twin pregnancies: cell-free DNA test contingent on results from the combined test.(Ultrasound in Obstetrics and Gynecology, 2018) Galeva, Slavyana; Konstantinidou, Liountmila; Gil Mira, María del Mar; Akolekar, Ranjit; Nicolaides, Kypros H.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.Item 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 and Gynecology, 2019) Gil Mira, María del Mar; Galeva, Slavyana; Jani, Jacques; Konstantinidou, Liountmila; Akolekar, Ranjit; Plana, María Nieves; Nicolaides, Kypros H.Objective: To report on the routine clinical implementation of cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancies and to define the performance of the test by combining our results with those arising from systematic review of the literature. Methods: The data for the study were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10+0-14+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 in 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 ICTRP (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 pregnancies. Meta-analysis was then performed using our data and data from 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, 9 (90.0%) of 10 of trisomy 18, 1 (50.0%) of 2 of trisomy 13 and 963 (99.5%) of 968 cases without any of the three trisomies. The literature search identified 7 relevant studies, excluding our papers because their data are included in the current study. In the combined total of our study and the 7 studies identified by the literature search there were 56 trisomy 21 and 3,718 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 3,143 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 3 affected cases and 2 (66.7%) of these were detected by the cfDNA test at FPR of 0.19% (5/2,569). Conclusions: Performance of cfDNA testing for trisomies 21 in twin pregnancies is similar to that reported for singleton pregnancies. The number of cases of trisomies 18 and 13 is too small for accurate assessment of predictive performance of the cfDNA test.