Prognostic value of angiogenic markers in pregnancies with fetal growth restriction.

OBJECTIVE: Pregnancies with fetal growth restriction are at increased risk of preeclampsia. Angiogenic markers including soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by fetal growth restriction (FGR). The utility of these markers as a predictor of preeclampsia in women with growth-restricted fetuses is still uncertain. This study aims to evaluate the prognostic value of angiogenic markers for predicting the development of preeclampsia in pregnancies with FGR and suspected preeclampsia. METHODS: This study included 93 women with FGR, defined according to Delphi consensus criteria, who were assessed for angiogenic markers sFlt-1 and PlGF for suspicion of preeclampsia at the Department of Obstetrics and feto-maternal Medicine at the Medical University of Vienna between 2013 and 2020. Women with established diagnosis of preeclampsia at sampling were excluded. Cox regression analysis and logistic regression were performed to demonstrate the association of angiogenic markers with the outcome. RESULTS: Within this cohort, 14 women (15.1%) developed preeclampsia within one week from sampling, 21 (22.6%) within two weeks, 38 (40.9%) at any time. The sFLT-1/PLGF ratio consistently showed a stronger association with development of preeclampsia compared to sFlt-1 or PlGF alone in pregnancies with fetal growth restriction (PE within a week, AUC 0.85 vs 0.82 and 0.72, respectively). Models including sFlt-1/PlGF were more strongly associated with preeclampsia hazard compared to sFlt-1 and PlGF alone models (C-index: 0.79±0.046 vs 0.76±0.048 and 0.75±0.047, respectively). Risk classification capabilities of sFlt-1/PlGF decreased after the two-week time point. The established cut-off value for ruling out preeclampsia (sFlt-1/PlGF ratio <38) was effective with a negative predictive value of 93.3% and sensitivity of 95.2%. CONCLUSION: Combined use of sFlt-1/PlGF can be preferred to PlGF alone in pregnancies with fetal growth restriction. Moreover, established cut-offs for ruling-out development of preeclampsia seem to be effective in these patients. This article is protected by copyright. All rights reserved.

Longitudinal assessment of angiogenic markers in prediction of adverse outcome in women with confirmed pre-eclampsia.

OBJECTIVES: Angiogenic marker assessment, such as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF), is known to be a useful tool in the prediction of pre-eclampsia (PE). However, evidence from surveillance strategies in pregnancies with a PE diagnosis is lacking. Therefore, we aimed to assess the predictive performance of longitudinal maternal serum angiogenic marker assessment for both maternal and perinatal adverse outcomes when compared to standard laboratory parameters in pregnancies with confirmed PE. METHODS: This was a retrospective analysis of prospectively collected data from January 2013 to December 2020 at the Medical University of Vienna. The inclusion criteria were singleton pregnancy with confirmed PE and post-diagnosis maternal serum angiogenic marker assessment at a minimum of two timepoints. The primary outcome was the predictive performance of longitudinal sFlt-1 and PlGF assessment for adverse maternal and perinatal outcomes compared to conventional laboratory monitoring at the same time in pregnancies with confirmed PE. Composite adverse maternal outcome included intensive care unit admission, pulmonary edema, eclampsia and/or death. Composite adverse perinatal outcome included stillbirth, neonatal death, placental abruption, neonatal intensive care unit admission, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome and/or mechanical ventilator support. RESULTS: In total, 885 post-diagnosis sFlt-1/PlGF ratio measurements were obtained from 323 pregnant women with confirmed PE. For composite adverse maternal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt-1/PlGF ratio (area under the receiver-operating-characteristics curve (AUC), 0.72 (95% CI, 0.62-0.81)), creatinine (AUC, 0.71 (95% CI, 0.62-0.81)) and lactate dehydrogenase (LDH) levels (AUC, 0.73 (95% CI, 0.65-0.81)). Maternal platelet levels (AUC, 0.65 (95% CI, 0.55-0.74)), serum alanine aminotransferase (ALT) (AUC, 0.59 (95% CI, 0.49-0.69)) and aspartate aminotransferase (AST) (AUC, 0.61 (95% CI, 0.51-0.71) levels had poor standalone predictive accuracy. The best prediction model consisted of a combination of maternal serum LDH, creatinine levels and sFlt-1/PlGF ratio, which had an AUC of 0.77 (95% CI, 0.68-0.85), significantly higher than sFlt-1/PlGF ratio alone (P = 0.037). For composite adverse perinatal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt-1/PlGF ratio (AUC, 0.82 (95% CI, 0.75-0.89)) and creatinine (AUC, 0.74 (95% CI, 0.67-0.80)) levels, sFlt-1/PlGF ratio being superior to creatinine alone (P < 0.001). Maternal serum LDH levels (AUC, 0.65 (95% CI, 0.53-0.74)), platelet count (AUC, 0.57 (95% CI, 0.44-0.67)), ALT (AUC, 0.58 (95% CI, 0.48-0.67)) and AST (AUC, 0.58 (95% CI, 0.48-0.67)) levels had poor standalone predictive accuracy. No combination of biomarkers was superior to maternal serum sFlt-1/PlGF ratio alone for prediction of composite adverse perinatal outcome (P > 0.05 for all). CONCLUSIONS: In pregnancies with confirmed PE, longitudinal maternal serum angiogenic marker assessment is a good predictor of adverse maternal and perinatal outcomes and superior to some conventional laboratory parameters. Further studies should focus on optimal surveillance following diagnosis of PE. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Growth temperature induced changes of luminescence in epitaxial BN: from colour centres to donor-acceptor recombination.

Defects play a very important role in semiconductors and only the control over the defect properties allows the implementation of materials in dedicated applications. We present an investigation of the UV luminescence of defects in hexagonal boron nitride (h-BN) grown by Metal Organic Vapor Phase Epitaxy (MOVPE). Such intentionally introduced defects are important for applications like deep UV emission and quantum information. In this work, we performed photoluminescence and cathodoluminescence experiments on a set of h-BN layers grown by MOVPE at different growth temperatures (tgr). The obtained defect-related spectra in the ultraviolet range include well-known lines at about 230 nm (X230, hν = 5.4 eV) and 300 nm (C300 - the brightest one, hν = 4.14 eV) as well as a rarely observed band with a zero-phonon line at 380 nm (C380, hν = 3.24 eV). The C300 and C380 bands have the characteristic of a color centre showing sharp lines (0.6 nm width) at 5 K. These lines are most probably an internal transition of carbon-related defects. We show that for samples grown at high temperatures (tgr > 1200 °C), the lines related to the color centres C are replaced by broad bands at 330 nm and 400 nm, which we marked as D330 and D400, respectively. The D bands have similar central energies to the C bands but extend over a large energy range, so we propose that the D emission is due to a shallow donor to deep acceptor recombination. Time-resolved photoluminescence analysis determined the lifetimes of the individual lines in the range from 0.9 ns (C300), 1.8 ns (C380) to 4 ns (D400). The C300 and C380 color centre bands are composed of a series of characteristic lines that are due to the interaction with phonons. The E1u (198 meV) and A2u (93 meV) phonon replicas have been identified.

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ganglionic eminence: volumetric assessment of transient brain structure utilizing fetal magnetic resonance imaging.

OBJECTIVE: To provide quantitative magnetic resonance imaging (MRI) super-resolution-based three-dimensional volumetric reference data on the growth dynamics of the ganglionic eminence (GE) relative to cortical and total fetal brain volumes (TBV). METHODS: This was a retrospective study of fetuses without structural central nervous system anomalies or other confounding comorbidities that were referred for fetal MRI. Super-resolution reconstructions of 1.5- and 3-Tesla T2-weighted images were generated. Semiautomatic segmentation of TBV and cortical volume and manual segmentation of the GE were performed. Cortical volume, TBV and GE volume were quantified and three-dimensional reconstructions were generated to visualize the developmental dynamics of the GE. RESULTS: Overall, 120 fetuses that underwent 127 MRI scans at a mean gestational age of 27.23 ± 4.81 weeks (range, 20-37 weeks) were included. In the investigated gestational-age range, GE volume ranged from 74.88 to 808.75 mm3 and was at its maximum at 21 gestational weeks, followed by a linear decrease (R2 = 0.559) throughout the late second and third trimesters. A pronounced reduction in GE volume relative to cortical volume and TBV occurred in the late second trimester, with a decline in this reduction observed in the third trimester (R2 = 0.936 and 0.924, respectively). Three-dimensional rendering allowed visualization of a continuous change in the shape and size of the GE throughout the second and third trimesters. CONCLUSIONS: Even small compartments of the fetal brain, which are not easily accessible by standardized two-dimensional modalities, can be assessed precisely by super-resolution processed fetal MRI. The inverse growth dynamics of GE volume compared with TBV and cortical volume reflects the transitory nature and physiological involution of this (patho-)physiologically important brain structure. The normal development and involution of the GE is mandatory for normal cortical development. Pathological changes of this transient organ precede impairment of cortical structures, and their detection may allow an earlier diagnosis of such anomalies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Temperature induced giant shift of phonon energy in epitaxial boron nitride layers.

The recent progress in the growth of large-area boron nitride epilayers opens up new possibilities for future applications. However, it remains largely unclear how weakly attached two-dimensional BN layers interact with their substrate and how their properties are influenced by defects. In this work, we investigate hBN layers grown by metal organic vapor phase epitaxy using Fourier-transform infrared spectroscopy in the temperature range of 160-540 K. Our measurements reveal strong differences in the character of layer-substrate interaction for as-grown and delaminated epitaxial layers. A much weaker interaction of as-grown layers is explained by wrinkles formation that reduces strain at the layer-substrate interface, which for layers transferred to other substrates occurs only in a limited temperature range. The most striking result is the observation of a giant increase in theE1uphonon energy of up to ∼6 cm-1in a narrow temperature range. We show that the amplitude and temperature range of the anomaly is strongly modified by UV light illumination. The observed giant effect is explained in terms of strain generation resulting from charge redistribution between shallow traps and different defects, which can be interpreted as a result of strong electron-phonon coupling in hBN. The observed narrow temperature range of the anomaly indicates that the effect may be further enhanced for example by electrostrictive effects, expected for sp2boron nitride.

Should angiogenic markers be included in diagnostic criteria of superimposed pre-eclampsia in women with chronic hypertension?

OBJECTIVE: Although the most recent guidance from the International Society for the Study of Hypertension in Pregnancy (ISSHP) has highlighted the role of angiogenic marker assessment in the diagnosis of pre-eclampsia (PE) in women with chronic hypertension, the ISSHP has withheld recommending its implementation due to the limited available evidence in this group of women. Therefore, we aimed to investigate the value of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) assessment in women with chronic hypertension and suspected superimposed PE. METHODS: This was a retrospective analysis of prospectively collected data recorded in an electronic database between January 2013 and October 2019. Women with chronic hypertension and singleton pregnancy who had suspected superimposed PE were included. Superimposed PE was suspected in women presenting with worsening hypertension, epigastric pain, new-onset edema, dyspnea or neurological symptoms. The exclusion criteria were delivery within 1 week after assessment for reasons other than PE, chronic kidney disease, history of cardiac disease, fetal aneuploidy, genetic syndrome or major structural anomaly and missing pregnancy outcome. Maternal serum angiogenic markers (sFlt-1, PlGF and sFlt-1/PlGF ratio) were measured. The primary outcome was the utility of angiogenic markers in the prediction of superimposed PE. Predictive accuracy was assessed for superimposed PE diagnosed at different timepoints, including within 1 week after assessment and any time before birth. The secondary outcome was comparison of adverse maternal and perinatal outcomes between women with superimposed PE diagnosed according to the traditional ISSHP criteria and those diagnosed according to extended criteria including angiogenic markers. The predictive accuracy of each angiogenic marker was assessed using receiver-operating-characteristics-curve analysis. Area under the curve (AUC) values were compared using De Long's test. A sensitivity analysis was planned for gestational age at assessment. The association of various variables with composite adverse maternal and perinatal outcomes was assessed using binomial regression. RESULTS: The study included 142 pregnant women with chronic hypertension and suspected superimposed PE, of whom 25 (17.6%) developed PE within 1 week after assessment, 52 (36.6%) developed PE at any timepoint before birth and 90 (63.4%) delivered without PE. Maternal serum angiogenic imbalance was associated significantly with superimposed PE diagnosed according to the ISSHP criteria within 1 week or at any time after assessment (P < 0.001 for both). The predictive accuracy of maternal serum sFlt-1/PlGF ratio for superimposed PE diagnosed within 1 week after assessment was superior to that of maternal serum PlGF level (AUC, 0.91 vs 0.86; P = 0.032). The addition of angiogenic imbalance to the traditional ISSHP diagnostic criteria was associated with an increase in the detection rate (35.1% increase; 95% credible interval (CrI), 16.6-53.6%) and positive (9.6% increase; 95% CrI, 0.0-20.6%) and negative (3.1% increase; 95% CrI, 1.3-4.9%) predictive values for composite adverse maternal outcome, with high posterior probabilities of an increase in each predictive accuracy parameter (> 99.9%, 95.6% and > 99.9%, respectively), without a meaningful decrease in specificity. The addition of angiogenic imbalance improved the detection rate for composite adverse perinatal outcome (20.6% increase; 95% CrI, 0.0-42.2%), with a high posterior probability (96.9%). There was a corresponding drop in specificity (5.7% decrease; 95% CrI, -2.3% to 13.6%), with a posterior probability of 91.8%. CONCLUSIONS: In women with chronic hypertension and suspected superimposed PE, addition of maternal serum angiogenic markers to the traditional diagnostic criteria for superimposed PE improved significantly the sensitivity for the prediction of both maternal and perinatal adverse outcomes. Implementation of angiogenic marker assessment in the evaluation of pregnant women with chronic hypertension should therefore be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Mapping Human Fetal Brain Maturation In Vivo Using Quantitative MRI.

BACKGROUND AND PURPOSE: On the basis of a single multidynamic multiecho sequence acquisition, SyMRI generates a variety of quantitative image data that can characterize tissue-specific properties. The aim of this retrospective study was to evaluate the feasibility of SyMRI for the qualitative and quantitative assessment of fetal brain maturation. MATERIALS AND METHODS: In 52 fetuses, multidynamic multiecho sequence acquisitions were available. SyMRI was used to perform multidynamic multiecho-based postprocessing. Fetal brain maturity was scored qualitatively on the basis of SyMRI-generated MR imaging data. The results were compared with conventionally acquired T1-weighted/T2-weighted contrasts as a standard of reference. Myelin-related changes in T1-/T2-relaxation time/relaxation rate, proton density, and MR imaging signal intensity of the developing fetal brain stem were measured. A Pearson correlation analysis was used to detect correlations between the following: 1) the gestational age at MR imaging and the fetal brain maturity score, and 2) the gestational age at MR imaging and the quantitative measurements. RESULTS: SyMRI provided images of sufficient quality in 12/52 (23.08%) (range, 23 + 6-34 + 0) fetal multidynamic multiecho sequence acquisitions. The fetal brain maturity score positively correlated with gestational age at MR imaging (SyMRI: r = 0.915, P < .001/standard of reference: r = 0.966, P < .001). Myelination-related changes in the T2 relaxation time/T2 relaxation rate of the medulla oblongata significantly correlated with gestational age at MR imaging (T2-relaxation time: r = -0.739, P = .006/T2-relaxation rate: r = 0.790, P = .002). CONCLUSIONS: Fetal motion limits the applicability of multidynamic multiecho-based postprocessing. However, SyMRI-generated image data of sufficient quality enable the qualitative assessment of maturity-related changes of the fetal brain. In addition, quantitative T2 relaxation time/T2 relaxation rate mapping characterizes myelin-related changes of the brain stem prenatally. This approach, if successful, opens novel possibilities for the evaluation of structural and biochemical aspects of fetal brain maturation.

Towards practical applications of quantum emitters in boron nitride.

We demonstrate quantum emission capabilities from boron nitride structures which are relevant for practical applications and can be seamlessly integrated into a variety of heterostructures and devices. First, the optical properties of polycrystalline BN films grown by metalorganic vapour-phase epitaxy are inspected. We observe that these specimens display an antibunching in the second-order correlation functions, if the broadband background luminescence is properly controlled. Furthermore, the feasibility to use flexible and transparent substrates to support hBN crystals that host quantum emitters is explored. We characterise hBN powders deposited onto polydimethylsiloxane films, which display quantum emission characteristics in ambient environmental conditions.

Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal haemodynamic function differs in pre-eclampsia when it is associated with a small-for-gestational-age newborn: a prospective cohort study.

OBJECTIVE: To describe maternal haemodynamic differences in gestational hypertension with small-for-gestational-age babies (HDP + SGA), gestational hypertension with appropriate-for-gestational-age babies (HDP-only) and control pregnancies. DESIGN: Prospective cohort study. SETTING: Tertiary Hospital, UK. POPULATION: Women with gestational hypertension and healthy pregnant women. METHODS: Maternal haemodynamic indices were measured using a non-invasive Ultrasound Cardiac Output Monitor (USCOM-1A® ) and corrected for gestational age and maternal characteristics using device-specific reference ranges. MAIN OUTCOME MEASURES: Maternal cardiac output, stroke volume, systemic vascular resistance. RESULTS: We included 114 HDP + SGA, 202 HDP-only and 401 control pregnancies at 26-41 weeks of gestation. There was no significant difference in the mean arterial blood pressure (110 versus 107 mmHg, P = 0.445) between the two HDP groups at presentation. Pregnancies complicated by HDP + SGA had significantly lower median heart rate (76 versus 85 bpm versus 83 bpm), lower cardiac output (0.85 versus 0.98 versus 0.97 MoM) and higher systemic vascular resistance (1.4 versus 1.0 versus 1.2 MoM) compared with control and HDP-only pregnancies, respectively (all P < 0.05). CONCLUSION: Women with HDP + SGA present with more severe haemodynamic dysfunction than HDP-only. Even HDP-only pregnancies exhibit impaired haemodynamic indices compared with normal pregnancies, supporting a role of the maternal cardiovascular system in gestational hypertension irrespective of fetal size. Central haemodynamic changes may play a role in the pathogenesis of pre-eclampsia and should be considered alongside placental aetiology. TWEETABLE ABSTRACT: Hypertensive disorders of pregnancy are associated with worse maternal haemodynamic function when associated with small-for-gestational-age birth.

Maternal arterial stiffness in hypertensive pregnancies with and without small-for-gestational-age neonate.

OBJECTIVE: Pregnancies complicated by pre-eclampsia with a small-for-gestational-age (SGA) neonate have poorer maternal hemodynamic function compared to those with hypertensive disorders of pregnancy (HDP) and an appropriately grown neonate. Arterial stiffness is a recognized prognostic marker of cardiovascular disease in the general population. The aim of this study was to compare maternal arterial stiffness between hypertensive pregnancies with, and those without, a SGA neonate and normotensive control pregnancies. METHODS: This was a prospective cohort study of pregnancies complicated by pre-eclampsia or gestational hypertension and healthy normotensive control pregnancies, presenting to a tertiary referral hospital between January 2012 and May 2018. Maternal arterial stiffness was assessed by aortic pulse-wave velocity (PWV) and aortic augmentation index (AIx), which were recorded using a non-invasive device (Arteriograph®). Maternal and hemodynamic factors were adjusted for using linear regression analysis. Pregnancies with HDP were divided into those that delivered a SGA (birth weight < 10th percentile) neonate (HDP + SGA group) and those that delivered an appropriately grown neonate (HDP-only group). Comparisons between groups were carried out using the Mann-Whitney U-test for continuous variables and the chi-square (or Fisher's exact) test for categorical variables. RESULTS: Included in the analysis were 69 patients with HDP who delivered a SGA neonate, 129 with HDP who delivered a normally grown neonate and 220 healthy controls. Maternal age, weight, height and heart rate were associated significantly with brachial and aortic AIx. Maternal weight, height, mean arterial pressure, heart rate and gestational age were significant predictors of aortic PWV. Adjusted aortic AIx was significantly higher in both the HDP + SGA and HDP-only groups, compared with in controls (12.5% and 10.0% vs 7.6%; both P < 0.01), and was significantly different between the two HDP groups (P = 0.002). Adjusted PWV was significantly higher in the HDP-only group compared with in controls and the HDP + SGA group (7.7 m/s vs 7.1 m/s and 7.1 m/s; both P < 0.001). Conversely, unadjusted PWV was not significantly different between the two HDP groups (P = 0.414). CONCLUSIONS: Pregnancies complicated by HDP with, and those without, a SGA neonate have significantly higher aortic AIx compared with uncomplicated normotensive pregnancies. Aortic AIx was highest in those pregnancies complicated by HDP with a SGA neonate, reflecting a progression in severity of arterial stiffness abnormality with a worsening clinical picture. These findings most likely reflect systemic reduced vascular compliance and increased systemic vascular resistance in pregnancy complicated by HDP. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Bulk and grain boundary Li-diffusion in dense LiMn2O4 pellets by means of isotope exchange and ToF-SIMS analysis.

Lithium diffusion in LiMn2O4 pellets is studied by means of isotope exchange and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). A 6Li-enriched film deposited by Pulsed Laser Deposition (PLD) on a dense LiMn2O4 pellet with natural abundance of lithium isotopes is used to study the tracer diffusion of lithium. The measured profiles are analyzed by numerical models describing the 6Li tracer diffusion from the film into the pellet. Experiments in the Harrison type B regime of diffusion kinetics allow for the distinction and simultaneous determination of bulk and grain boundary diffusion coefficients. Changing the experimental conditions to reach Harrison type A behavior yields effective diffusion coefficients for lithium tracer diffusion in LiMn2O4. Activation energies for bulk and grain boundary diffusion were obtained from experiments at different temperatures. Our values are critically compared to previous studies.

Upconverted electroluminescence via Auger scattering of interlayer excitons in van der Waals heterostructures.

The intriguing physics of carrier-carrier interactions, which likewise affect the operation of light emitting devices, stimulate the research on semiconductor structures at high densities of excited carriers, a limit reachable at large pumping rates or in systems with long-lived electron-hole pairs. By electrically injecting carriers into WSe2/MoS2 type-II heterostructures which are indirect in real and k-space, we establish a large population of typical optically silent interlayer excitons. Here, we reveal their emission spectra and show that the emission energy is tunable by an applied electric field. When the population is further increased by suppressing the radiative recombination rate with the introduction of an hBN spacer between WSe2 and MoS2, Auger-type and exciton-exciton annihilation processes become important. These processes are traced by the observation of an up-converted emission demonstrating that excitons gaining energy in non-radiative Auger processes can be recovered and recombine radiatively.

Prediction of adverse pregnancy outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction.

OBJECTIVE: To identify key factors associated with adverse perinatal outcome in monochorionic diamniotic twin pregnancy complicated by selective fetal growth restriction (sFGR). METHODS: This was a retrospective cohort study of all monochorionic diamniotic twin pregnancies diagnosed with sFGR at ≥ 16 weeks' gestation, in a single tertiary referral center between March 2000 and May 2015. The presence of coexisting twin-twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including those of the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow in the UA of the smaller twin. DV pulsatility indices for veins (DV-PIV) were converted to Z-scores and estimated fetal weight values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome, which was defined according to survival and included both intrauterine fetal demise and neonatal death of the FGR twin. RESULTS: We analyzed 104 pregnancies, of which 66 (63.5%) were diagnosed with Type-I and 38 (36.5%) with Type-II sFGR at initial presentation. In pregnancies complicated by Type-II sFGR, the diagnosis of sFGR was made earlier than in those complicated by Type-I sFGR (mediam GA, 19.6 vs 21.5 weeks; P = 0.012), and Type-II sFGR was associated with increased risk of adverse perinatal outcome (intrauterine demise of the smaller twin, 34.2% vs 10.6%; P = 0.004). Twin pregnancies complicated by sFGR resulting in perinatal demise had a significantly earlier diagnosis (P = 0.002) and lower birth-weight centile of the smaller twin (P < 0.01), those with Type-I sFGR had earlier GA at delivery (P = 0.007) and those with Type-II sFGR had higher DV-PIV Z-score of the smaller twin (P = 0.003), when compared with pregnancies resulting in live birth. Coexisting TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR (P > 0.05 for both). Earlier GA at diagnosis (hazard ratio (HR), 0.70 (95% CI, 0.56-0.88); P = 0.002), Type-II sFGR (HR, 3.53 (95% CI, 1.37-9.07); P = 0.008) and higher DV-PIV Z-score (HR, 1.36 (95% CI, 1.12-1.65); P = 0.001) were significantly associated with increased risk of adverse perinatal outcome of the smaller twin. CONCLUSIONS: Pregnancies complicated by Type-II sFGR are diagnosed significantly earlier and are associated with increased risk of adverse perinatal outcome compared with those with Type-I sFGR. Coexisting TTTS has no significant impact on the perinatal outcome of pregnancies diagnosed with either Type-I or Type-II sFGR. Earlier GA at diagnosis, Type-II sFGR and higher DV-PIV Z-score are associated significantly with increased risk of adverse perinatal outcome of the smaller twin. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies. METHODS: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. RESULTS: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation. CONCLUSIONS: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Intraoperative superficial inferior epigastric vein preservation for venous compromise prevention in breast reconstruction by deep inferior epigastric perforator flap.

OBJECTIVE: The aim of this study was to analyze our technique of intraoperative venous compromise management based on conservation of the superficial inferior epigastric vein (SIEV), and to undertake a retrospective review of our series of breast reconstructions by deep inferior epigastric perforator (DIEP) flap, followed by a review of other techniques reported in the literature. MATERIALS AND METHODS: This retrospective study involves 198 breast reconstructions by DIEP flap performed between January 2010 and September 2017. Our surgical technique is related in detail, with a focus on venous compromise management. Operative time, re-intervention rate, hospital stay, and complications were all noted and analyzed, and a literature review dealt with other techniques of prevention and management of flap venous congestion. RESULTS: Among breast reconstructions by DIEP, 7.5% contained an episode of intraoperative venous compromise, as opposed to 6.5% postoperatively. The SIEV was used in 65% of cases of venous congestion. In our series, 15.1% of cases presented postoperative complications, and we observed a 2.5% flap failure rate (2%: venous thrombosis; 0.5%: arterial thrombosis). In all patients for whom venous drainage augmentation was performed, the flaps survived without partial loss. While average length of hospital stay in the group having undergone intraoperative secondary anastomosis was 7.5 days, in the group having undergone postoperative secondary anastomosis, it was 13.5 days. CONCLUSION: In cases of intraoperative venous congestion, while a second venous anastomosis may immediately increase duration of an initial intervention by 1hour and 45minutes, it is nonetheless likely to pronouncedly decrease need for surgical revision, cases of failure, rate of partial necrosis and overall hospital stay.

Perinatal loss at term: role of uteroplacental and fetal Doppler assessment.

OBJECTIVE: To examine the associations of uterine artery (UtA) Doppler indices and cerebroplacental ratio (CPR) with perinatal outcome at term. METHODS: This was a retrospective cohort study conducted at a tertiary referral center that included all singleton pregnancies undergoing ultrasound assessment in the third trimester that subsequently delivered at term. Fetal biometry and Doppler assessment, including that of the umbilical artery (UA), fetal middle cerebral artery (MCA) and UtA, were recorded. Data were corrected for gestational age, and CPR was calculated as the ratio of MCA pulsatility index (PI) to UA-PI. Logistic regression analysis was conducted to examine for independent predictors of adverse perinatal outcome. RESULTS: The study included 7013 pregnancies, 12 of which were complicated by perinatal death. When compared with pregnancies resulting in perinatal survival, pregnancies complicated by perinatal death had a significantly higher proportion of small-for-gestational-age infants (25.0% vs 5%; P = 0.001) and a higher incidence of low (< 5th centile) CPR (16.7% vs 4.5%; P = 0.041). A subgroup analysis comparing 1527 low-risk pregnancies that resulted in fetal survival with pregnancies complicated by perinatal death demonstrated that UtA-PI multiples of the median (MoM), CPR < 5th centile and estimated fetal weight (EFW) centile were all associated significantly with the risk of perinatal death at term (all P < 0.05). After adjusting for confounding variables, only EFW centile (odds ratio (OR) 0.96 (95% CI, 0.93-0.99); P = 0.003) and UtA-PI MoM (OR 13.10 (95%CI, 1.95-87.89); P = 0.008) remained independent predictors of perinatal death in the low-risk cohort. CONCLUSION: High UtA-PI at term is associated independently with an increased risk of adverse perinatal outcome, regardless of fetal size. These results suggest that perinatal mortality at term is related not only to EFW and fetal redistribution (CPR), but also to indices of uterine perfusion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Reduced fetal movements and cerebroplacental ratio: evidence for worsening fetal hypoxemia.

OBJECTIVE: To investigate the fetal cerebroplacental ratio (CPR) in women presenting with reduced fetal movements (RFM). METHODS: This was a retrospective cohort study of data collected over an 8-year period at a fetal medicine unit at a tertiary referral center. The cohort comprised 4500 singleton pregnancies presenting with RFM at or after 36 weeks' gestation and 1527 control pregnancies at a similar gestational age without RFM. Fetal biometry and Doppler parameters were recorded and converted into centiles and multiples of the median (MoM). CPR was defined as the ratio between the fetal middle cerebral artery (MCA) pulsatility index (PI) and the umbilical artery (UA) PI. Subgroup analysis for fetal size and for single vs multiple episodes of RFM was performed. RESULTS: Compared with controls, pregnancies with RFM had lower MCA-PI MoM (median, 0.95 vs 0.97; P < 0.001) and CPR MoM (median, 0.97 vs 0.99; P = 0.018). Compared with women presenting with single episodes of RFM, pregnancies with multiple episodes (≥ 2 episodes) had lower CPR MoM (median, 0.94 vs 0.98; P = 0.003). On subgroup analysis for fetal size, compared with controls, appropriate-for-gestational-age fetuses in the RFM group had lower MCA-PI MoM (median, 0.96 vs 0.97; P = 0.003) and higher rate of CPR below the 5th centile (5.3% vs 3.6%; P = 0.015). Logistic regression analysis demonstrated an association of risk of recurrent RFM with maternal age (OR, 0.96; 95% CI, 0.93-0.99), non-Caucasian ethnicity (OR, 0.72; 95% CI, 0.53-0.97), estimated fetal weight centile (OR, 1.01; 95% CI, 1.00-1.02) and CPR MoM (OR, 0.24; 95% CI, 0.12-0.47). CONCLUSION: Pregnancies complicated by multiple episodes of RFM show significantly lower CPR MoM and MCA-PI MoM compared with those with single episodes and controls. This is likely to be due to worsening fetal hypoxemia in women presenting with recurrent RFM. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.