Publications by authors named "R Akolekar"

191 Publications

Reference Ranges for the Pulsed wave Doppler of the Fetal Cardiac Inflow and Outflow Tracts from 13 to 36 Weeks Gestation: Short title: Zidere, Fetal inflow and outflow tract, Pulsed wave Doppler, z scores.

J Am Soc Echocardiogr 2021 May 3. Epub 2021 May 3.

Medway Fetal and Maternal Medicine Centre, Medway Maritime Hospital, Gillingham, Kent, United Kingdom; Institute of Medical Sciences, Canterbury Christ Church University, Rowan William's Court, Chatham, Kent ME4 4UF.

Objective: Doppler assessment ventricular filling and outflow tract velocities are an integral part of the fetal echocardiogram, to assess diastolic function, systolic function and outflow tract obstruction. There is a paucity of prospective data from a large sample of normal fetuses in the published literature. We report reference ranges for pulsed wave Doppler flow of the mitral valve, tricuspid valve, aortic valve and pulmonary valve as well as heart rate, in a large number of fetuses prospectively examined at a single tertiary fetal cardiology centre.

Methods: The study population comprised 7885 fetuses at 13 to 36 weeks' gestation with no detectable abnormalities from pregnancies resulting in normal live births. Prospective pulsed wave Doppler blood flow measurements were taken of the mitral, tricuspid, aortic and pulmonary valves. The fetal heart rate was recorded at the time of each assessment. Regression analysis, with polynomial terms to assess for linear and nonlinear contributors, was used to establish the relationship between each measurement and gestational age.

Results: The measurement for each cardiac Doppler measurement was expressed as a z score (difference between observed and expected value divided by the fitted SD corrected for gestational age) and percentile. Analysis included calculation of gestation-specific SDs. Regression equations are provided for the cardiac inflow and outflow tracts.

Conclusions: The study establishes reference ranges for fetal cardiac Doppler measurements and heart rate between 13 to 36 weeks' gestation that may be useful in clinical practice.
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http://dx.doi.org/10.1016/j.echo.2021.04.017DOI Listing
May 2021

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

Fetal fraction of cell free DNA in screening for hypertensive disorders at 11-13 weeks.

J Matern Fetal Neonatal Med 2021 Jan 31:1-6. Epub 2021 Jan 31.

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

Objective: To investigate whether first-trimester maternal plasma fetal fraction is altered in women that subsequently develop preeclampsia (PE) or gestational hypertension (GH) and to examine its potential value in improving the performance of screening for PE and GH by maternal factors and maternal serum pregnancy associated plasma protein-A (PAPP-A), mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI).

Methods: The study population of 10,131 pregnancies undergoing cell free fetal DNA testing at 11-13 weeks' gestation included 91 (0.9%) cases with preterm-PE, 222 (2.2%) cases with term-PE, 360 (3.6%) with GH and 9,458 (93.4%) cases unaffected by hypertensive disorders. Maternal plasma fetal fraction levels were expressed as multiples of the median (MoM) after adjustment for maternal factors and crown-rump length. The performance of screening for preterm-PE, term PE and GH by maternal factors and MoM values of fetal fraction, PAPP-A, UtA-PI and MAP was evaluated by receiver operating characteristic (ROC) curves.

Results: The median fetal fraction MoM was significantly lower in the preterm-PE (0.825; IQR 0.689-1.115 MoM,  < .001), term-PE (0.946; IQR 0.728-1.211 MoM,  = .028) and GH (0.928; IQR 0.711-1.182 MoM,  < .001) groups than in the unaffected group (1.002; IQR 0.785-1.251 MoM). However, the performance of screening for PE or GH by maternal factors alone or by maternal factors and PAPP-A, UtA-PI and MAP was not significantly improved by the addition of fetal fraction.

Conclusions: First trimester maternal plasma fetal fraction is not useful in screening for hypertensive disorders of pregnancy.
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http://dx.doi.org/10.1080/14767058.2021.1879043DOI Listing
January 2021

Reply.

Ultrasound Obstet Gynecol 2020 Dec;56(6):953-954

Fetal Medicine Unit, Medway Maritime Hospital, Gillingham, UK.

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http://dx.doi.org/10.1002/uog.22150DOI Listing
December 2020