Publications by authors named "S Galeva"

8 Publications

Cell-free DNA testing of maternal blood in screening for trisomies in twin pregnancy: cohort study at 10-14 weeks and updated meta-analysis.

Ultrasound Obstet Gynecol 2021 Apr 10. Epub 2021 Apr 10.

Harris Birthright Research Centre of Fetal Medicine, King's College Hospital, London, UK.

Objective: To expand the limited knowledge on cell-free (cf)DNA analysis of maternal blood for trisomies 21, 18 and 13 in twin pregnancies by updating the data from the Fetal Medicine Foundation (FMF) on prospective first trimester screening and those arising from systematic review of the literature.

Methods: The FMF data were derived from prospective screening for trisomies 21, 18 and 13 in twin pregnancies at 10 -14 weeks' gestation using the Harmony® prenatal test of Roche/Ariosa Diagnostics, Inc. 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, irrespective of gestational age at testing, in which data on pregnancy outcome were provided for more than 85% of the study population. Meta-analysis was then performed using the FMF data and data from the studies identified by the literature search. This review was registered in PROSPERO international database for systematic reviews RESULTS: In 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) cases there was prenatal or postnatal karyotyping or the birth of phenotypically normal babies; 95 cases were excluded from further analysis either because the pregnancies 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, 2 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, 9 (90.0%) of 10 of trisomy 18, 1 (50.0%) of 2 of trisomy 13 and 1235 (99.6%) of 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 total 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.

Conclusions: In twin pregnancies the reported DR of trisomy 21 by cfDNA testing is high, but lower than in singleton pregnancies, whereas the FPR appears to be equally low. The number of cases of trisomy 18 and more so trisomy 13 is too small for accurate assessment of the predictive performance of the cfDNA test. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/uog.23648DOI Listing
April 2021

Placental function and fetal weight are associated with maternal hemodynamic indices in uncomplicated pregnancies at 35-37 weeks of gestation.

Am J Obstet Gynecol 2020 06 15;222(6):604.e1-604.e10. Epub 2020 Jan 15.

Harris Birthright Research Centre for Fetal Medicine, Fetal Medicine Research Institute, King's College London, London, United Kingdom; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.

Background: Over the years, there has been an increasing interest in the assessment of maternal hemodynamic responses during pregnancy. With the use of both noninvasive devices and/or maternal echocardiography, it has been shown that mothers who have pregnancy complications have altered hemodynamics compared with those who have uncomplicated pregnancies. It also has been suggested that preexisting maternal cardiac changes might drive the development of complications in pregnancy that are associated with impaired placentation. To understand, however, this potential link in complicated pregnancies, it is important to clarify whether placental function is associated with maternal cardiac functional indices in normal pregnancies.

Objective: To determine whether placental function, perfusion, and fetal weight are associated with maternal cardiac hemodynamic responses at 35-36 weeks of gestation in normal pregnancies.

Study Design: Prospective screening of women attending Kings' College Hospital for routine hospital visit at 35-37 weeks' gestation. We recorded maternal characteristics and measured mean arterial pressure, uterine artery pulsatility index, sonographic estimated fetal weight, and serum placental growth factor and soluble fms-like tyrosine kinase 1. We also performed maternal echocardiogram to assess cardiac output and peripheral vascular resistance as well as indices of diastolic and systolic function, including global longitudinal systolic function and left ventricular mass indexed to body surface area.

Results: We studied 1386 women. Maternal characteristics were associated with both maternal hemodynamics and functional and structural indices. Uterine artery pulsatility index was associated with left ventricular mass (P=.03) and global longitudinal systolic function (P=.017). There were significant nonlinear associations between placental growth factor and cardiac output and peripheral vascular resistance (P<.001 for both) and between soluble fms-like tyrosine kinase 1 and peripheral vascular resistance (P=.018). Estimated fetal weight was associated with maternal cardiac output (mean increase=0.186, 95% confidence interval, 0.133-0.238, P<.001) and peripheral vascular resistance (mean decrease=-0.164, 95% confidence interval, -0.217 to -0.111, P<.001). No association was noted between placental and fetal parameters and maternal cardiac functional and structural indices. In multivariable analysis, placental growth factor remained strongly associated with maternal cardiac output and peripheral vascular resistance (P=.002 for both) over and above maternal characteristics and estimated fetal weight. Estimated fetal weight was associated with left ventricular mass (0.102, 95% confidence interval, 0.044-0.162, P=.001).

Conclusion: The results of this study suggest a strong link between maternal hemodynamic responses and fetoplacental needs across the whole spectrum in normal pregnancies. These findings would also indicate that to diagnose maternal cardiac dysfunction in pregnancies complicated by impaired placentation a more extensive echocardiographic assessment might be needed rather than relying on hemodynamics which are strongly associated with fetoplacental indices.
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http://dx.doi.org/10.1016/j.ajog.2020.01.011DOI Listing
June 2020

First-trimester screening-biomarkers and cell-free DNA.

J Matern Fetal Neonatal Med 2019 Dec 8:1-7. Epub 2019 Dec 8.

Department of Obstetrics and Gynaecology, Institute of Child and Maternal Care "Alfred Rusescu", Bucharest, Romania.

The introduction of cell-free DNA into clinical practice has changed the screening approach. Healthcare professionals and future parents tend to overestimate NIPT (noninvasive prenatal testing) capabilities despite its relatively high cost and limited information. In this review, our aim was to survey how various countries have introduced contingent screening models and to discuss the advantages and disadvantages of the combined screening test and the use of NIPT. The Web of Science, PubMed database and institutional websites were searched for information regarding screening approaches and the implementation in different countries. There are nine countries and regions that have already approved contingent screening test, while others (e.g. Australia) are discussing the implementation of contingent screening versus universal use of NIPT. There are several recent meta-analyses debating whether to use NIPT for universal screening for trisomies and other fetal conditions. NIPT is a reasonable option as an advanced screening test for trisomy 21, 18 and 13 only. Introducing screening by NIPT instead of a first-trimester screening will cause the loss of other valuable information including accurate dating of pregnancy, diagnosing major structural fetal abnormalities and multiple pregnancies at an early gestational age. Additionally, the opportunity to screen for early preeclampsia will be lost. Currently, the price for NIPT is still high adding extra strain on publicly funded health systems.
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http://dx.doi.org/10.1080/14767058.2019.1698031DOI Listing
December 2019

Non-Invasive Prenatal Testing beyond Trisomies.

J Med Life 2019 Jul-Sep;12(3):221-224

Department of Obstetrics and Gynecology, Alessandrescu-Rusescu Institute of Mother and Child Care, Bucharest, Romania.

The last decade has seen incredible advances in the genetic era, in next-generation sequencing of cell-free DNA in the maternal plasma, detecting abnormal fetal chromosomes. Non-invasive prenatal testing (NIPT) has showed increased sensitivity and specificity for Down syndrome superior to any other screening test. Technical advances have made possible the detection of other conditions which does not necessarily mean clinical benefit for the patient. Private laboratories have added multiple conditions in the panel of NIPT, but some of these abnormalities are so rare, that their prevalence is not even clear. Data regarding clinical performance of extended NIPT is lacking. Implementation of such a test has to be carefully weighed, and not only the benefits but also the harm should be taken into account.
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http://dx.doi.org/10.25122/jml-2019-0053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814886PMC
December 2019

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 06 4;53(6):734-742. Epub 2019 Jun 4.

Fetal Medicine Research Institute, King's College Hospital, London, UK.

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.
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http://dx.doi.org/10.1002/uog.20284DOI Listing
June 2019