Synthetic MRI and MR Fingerprinting-Derived Relaxometry of Antenatal Human Brainstem Myelination: A Postmortem-Based Quantitative Imaging Study.

BACKGROUND AND PURPOSE: The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. MATERIALS AND METHODS: In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. RESULTS: Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [r = -0.459; P = .021]; midbrain [r = -0.413; P = .040]), T2-relaxation times (medulla oblongata [r = -0.625; P < .001]; midbrain [r = -0.571; P = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [r = -0.433; P = .035]; midbrain [r = -0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =-0.883; P < .001]; midbrain [r = -0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain). CONCLUSIONS: There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

The Impact of COVID-19 during Pregnancy on Maternal Hemodynamic Function, Angiogenic Markers and Neonatal Outcome.

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in pregnancy are associated with the development of preeclampsia and fetal growth restriction (FGR). Recently, preeclampsia was linked to impaired maternal hemodynamic function. This retrospective study evaluated singleton pregnancies with COVID-19 during pregnancy and healthy pregnant controls matched for gestational age from November 2020 to March 2022. Non-invasive assessment of maternal hemodynamics by continuous wave Doppler ultrasound measurements (USCOM-1A® Monitor) and oscillometric arterial stiffness (Arteriograph) was performed. Overall, 69 pregnant women were included-23 women after COVID-19 during pregnancy and 46 healthy controls. While two women (8.7%) were admitted to the hospital due to COVID-19-related symptoms, none required intensive care unit admission or non-invasive/invasive ventilation. There were no statistically significant differences in the majority of hemodynamic parameters between the two cohorts. The prevalence of FGR was significantly higher in the COVID-19 during pregnancy group (9.5% vs. healthy controls: 0.0%; p = 0.036), especially in nulliparous women. No difference in angiogenic markers and neonatal outcomes were observed between pregnant women after COVID-19 and healthy controls. In conclusion, no significant differences in hemodynamic parameters or neonatal outcome were observed in women with COVID-19 during pregnancy. However, an increased prevalence of FGR could be described.

Revisiting the Pathophysiology of Intracranial Hemorrhage in Fetuses with Chiari II Malformation: Novel Imaging Biomarkers of Disease Severity?

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) has emerged as a notable concern in Chiari II malformation (CM II), yet its origins and clinical implications remain elusive. This study aims to validate the in utero prevalence of ICH in CM II and investigate contributing factors, and visualize the findings in a network format. MATERIALS AND METHODS: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II (presenting January 2007 to December 2022) was performed for ICH utilizing EPI-T2* blood-sensitive sequence. Fetuses with aqueduct stenosis (AS) were included as a control group. The incidence of ICH and corresponding gestational ages were compared between CM II and AS cases, and morphometric measurements (inner/outer CSF spaces, posterior fossa, venous structure) were compared among the 4 1:1 age-matched groups: CM II+ICH, CM II-ICH, AS+ICH, and AS-ICH. Additionally, a co-occurrence network was constructed to visualize associations between phenotypic features in ICH cases. RESULTS: A total of 101 fetuses with CM II and 90 controls with AS at a median gestational age of 24.4 weeks and 22.8 weeks (P = .138) were included. Prevalence of ICH in fetuses with CM II was higher compared with the AS cases (28.7% versus 18.9%, P = .023), accompanied by congested veins (deep vein congestion mainly in young fetuses, and cortical veins may also be affected in older fetuses). ICH was notably correlated with specific anatomic features, essentially characterized by reduced outer CSF spaces and clivus-supraocciput angle. The co-occurrence network analysis reveals complex connections including bony defects, small posterior fossa dimensions, vermis ectopia, reduced CSF spaces, as well as venous congestion and venous sinus stenosis as pivotal components within the network. CONCLUSIONS: The high prevalence of ICH-detected by fetal MRI-among fetuses with CM emphasizes the pathophysiologic importance of venous congestion, ICH, and vasogenic edema. As indicators of disease severity, these features may serve as helpful additional imaging biomarkers for the identification of potential candidates for fetal surgery.

Periconceptional Counselling in Women with Autoimmune Inflammatory Rheumatic Diseases.

Systemic autoimmune rheumatic diseases (SARDs) in pregnancy represent a complex challenge for both patients and healthcare providers. Timely preparation for pregnancy enables adequate disease control, thereby reducing the risk of disease flare and pregnancy complications. Interdisciplinary care starting from the pre-pregnancy period throughout pregnancy and during breastfeeding ensures better fetal and maternal outcomes. This review provides a comprehensive guide to pre-pregnancy counselling in SARDs, an overview of medication management strategies tailored to pregnancy, disease activity and pregnancy monitoring in patients, and the promotion of shared decision making between healthcare providers and patients. Guidelines from international organizations were selected to provide a basis for this review and guidance through the quintessential discussion points of care.

Multiparametric prenatal imaging characterization of fetal brain edema in Chiari II malformation might help to select candidates for fetal surgery.

OBJECTIVE: To identify brain edema in fetuses with Chiari II malformation using a multiparametric approach including structural T2-weighted, diffusion tensor imaging (DTI) metrics, and MRI-based radiomics. METHODS: A single-center retrospective review of MRI scans obtained in fetuses with Chiari II was performed. Brain edema cases were radiologically identified using the following MR criteria: brain parenchymal T2 prolongation, blurring of lamination, and effacement of external CSF spaces. Fractional anisotropy (FA) values were calculated from regions of interest (ROI), including hemispheric parenchyma, internal capsule, and corticospinal tract, and compared group-wise. After 1:1 age matching and manual single-slice 2D segmentation of the fetal brain parenchyma using ITK-Snap, radiomics features were extracted using pyradiomics. Areas under the curve (AUCs) of the features regarding discriminating subgroups were calculated. RESULTS: Ninety-one fetuses with Chiari II underwent a total of 101 MRI scans at a median gestational age of 24.4 weeks and were included. Fifty scans were visually classified as Chiari II with brain edema group and showed significantly reduced external CSF spaces compared to the nonedema group (9.8 vs. 18.3 mm, p < 0.001). FA values of all used ROIs were elevated in the edema group (p < 0.001 for all ROIs). The 10 most important radiomics features showed an AUC of 0.81 (95%CI: 0.71, 0.91) for discriminating between Chiari II fetuses with and without edema. CONCLUSIONS: Brain edema in fetuses with Chiari II is common and radiologically detectable on T2-weighted fetal MRI sequences, and DTI-based FA values and radiomics features provide further evidence of microstructure differences between subgroups with and without edema. CLINICAL RELEVANCE STATEMENT: A more severe phenotype of fetuses with Chiari II malformation is characterized by prenatal brain edema and more postnatal clinical morbidity and disability. Fetal brain edema is a promising prenatal MR imaging biomarker candidate for optimizing the risk-benefit evaluation of selection for fetal surgery. KEY POINTS: Brain edema of fetuses prenatally diagnosed with Chiari II malformation is a common, so far unknown, association. DTI metrics and radiomics confirm microstructural differences between the brains of Chiari II fetuses with and without edema. Fetal brain edema may explain worse motor outcomes in this Chiari II subgroup, who may substantially benefit from fetal surgery.

Persistent Hydrocephalus, Shunt, and Subglottic Stenosis in a Newborn with Plasminogen Deficiency due to Delayed Treatment with Plasminogen Concentrates: A Case Report.

INTRODUCTION: Here we present the case of a newborn baby boy with severe plasminogen deficiency causing occlusive hydrocephalus and ligneous conjunctivitis. CASE PRESENTATION: Shortly after birth, the hydrocephalus was treated with a ventriculoperitoneal shunt implantation. However, the child had to be readmitted soon afterward because of shunt obstruction. Subglottic microtrauma caused by the necessary intubations then led to another life-threatening complication - subglottic stenosis with pseudomembrane formation. Microsurgical removal had to be performed to secure the airway. Initially, regular plasma transfusions achieved slightly elevated plasminogen activity levels and short-term improvement of the respiratory situation. However, shunt dysfunction reoccurred, and alternative treatment options were needed. Since therapy with plasminogen concentrate is already available in the USA with encouraging results, this treatment option was organized in hopes of equally good results for this patient. Fortunately, under short-term substitution with plasminogen concentrates, the implantation of a new ventriculoperitoneal shunt was successful, and respiratory problems resolved. CONCLUSION: Plasminogen concentrates are critically needed in Europe and other parts of the world to improve the care of and prevent complications among patients with plasminogen deficiency.

Biweekly Versus Monthly Hyperimmune Globulin Therapy for Primary Cytomegalovirus Infection in Pregnancy.

Primary cytomegalovirus (CMV) infection during pregnancy is associated with an increased risk of congenital CMV (cCMV). Hyperimmune globulin (HIG) therapy has been proposed as a potential prophylaxis to reduce maternal-fetal transmission. Data on whether the administration of HIG every 2 weeks offers benefits over HIG administration every 4 weeks are lacking. This was a retrospective analysis including pregnant women with primary CMV infection diagnosed in the first or early second trimester between 2010 and 2022 treated with HIG every 4 weeks (300 IE HIG per kg) or every 2 weeks (200 IE HIG per kg), respectively. In total, 36 women (4 weeks: n = 26; 2 weeks: n = 10) and 39 newborns (4 weeks: n = 29; 2 weeks: n = 10) were included. The median gestational age at the first HIG administration was 13.1 weeks. There was no significant difference in the cCMV rates between the women who received HIG every 4 versus every 2 weeks (n = 8/24 [33.3%] vs. 3/10 [30.0%]; p = 0.850). An abnormal fetal ultrasound was present in three fetuses and fetal magnetic resonance imaging (MRI) anomalies in four fetuses were related to cCMV infection, with no significant difference in the frequency between the two groups. A larger study will be needed to determine whether HIG administration every 2 instead of every 4 weeks improves the maternal-fetal transmission rates.

Effects of Intrauterine Growth Restriction (IUGR) on Growth and Body Composition Compared to Constitutionally Small Infants.

(1) Intrauterine growth restriction (IUGR) is associated with multiple morbidities including growth restriction and impaired neurodevelopment. Small for gestational age (SGA) is defined as a birth weight <10th percentile, regardless of the etiology. The term is commonly used as a proxy for IUGR, but it may represent a healthy constitutionally small infant. Differentiating between IUGR and constitutionally small infants is essential for the nutritional management. (2) Infants born at <37 weeks of gestation between 2017 and 2022, who underwent body composition measurement (FFM: fat-free mass; FM: fat mass) at term-equivalent age, were included in this study. Infants with IUGR and constitutionally small infants (SGA) were compared to infants appropriate for gestational age (AGA). (3) A total of 300 infants (AGA: n = 249; IUGR: n = 40; SGA: n = 11) were analyzed. FFM (p < 0.001) and weight growth velocity (p = 0.022) were significantly lower in IUGR compared to AGA infants, but equal in SGA and AGA infants. FM was not significantly different between all groups. (4) The FFM Z-score was significantly lower in IUGR compared to AGA infants (p = 0.017). Being born constitutionally small compared to AGA had no impact on growth and body composition. These data showed that early aggressive nutritional management is essential in IUGR infants to avoid impaired growth and loss of FFM.

Catestatin-A Potential New Therapeutic Target for Women with Preeclampsia? An Analysis of Maternal Serum Catestatin Levels in Preeclamptic Pregnancies.

BACKGROUND: Catestatin has been identified as an important factor in blood pressure control in non-pregnant adults. A possible impact on the development of hypertensive disorders of pregnancy has been indicated. Data on catestatin levels in pregnancy are scarce. The aim of this study was to investigate a potential association of maternal serum catestatin levels to the pathogenesis of preeclampsia. METHODS: We evaluated serum catestatin levels of 50 preeclamptic singleton pregnancies and 50 healthy gestational-age-matched pregnancies included in the obstetric biobank registry of the Medical University of Vienna. Receiver operating characteristic curves and logistic regression models were performed to investigate an association between catestatin levels and development of preeclampsia. RESULTS: Catestatin levels were significantly decreased in women with preeclampsia compared to healthy controls (median CST: 3.03 ng/mL, IQR [1.24-7.21 ng/mL] vs. 4.82 ng/mL, IQR [1.82-10.02 ng/mL]; p = 0.010), indicating an association between decreased catestatin values and the development of preeclampsia. There was no significant difference in catestatin values between early-onset preeclampsia and late-onset preeclampsia. Modelling the occurrence of preeclampsia via logistic regression was improved when adding catestatin as a predictive factor. CONCLUSIONS: Decreased serum catestatin levels are associated with the presence of preeclampsia. Further investigations into the diagnostic value and possible therapeutic role of catestatin in preeclampsia are warranted.

Maternal haemodynamics in Hypertensive Disorders of Pregnancy under antihypertensive therapy (HyperDiP): study protocol for a prospective observational case-control study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are associated with a high incidence of maternal and perinatal morbidity and mortality. HDP, in particular pre-eclampsia, have been determined as risk factors for future cardiovascular disease. Recently, the common hypothesis of pre-eclampsia being a placental disorder was challenged as numerous studies show evidence for short-term and long-term cardiovascular changes in pregnancies affected by HDP, suggesting a cardiovascular origin of the disease. Despite new insights into the pathophysiology of HDP, concepts of therapy remain unchanged and evidence for improved maternal and neonatal outcome by using antihypertensive agents is lacking. METHODS AND ANALYSIS: A prospective observational case-control study, including 100 women with HDP and 100 healthy controls, which will assess maternal haemodynamics using the USCOM 1A Monitor and Arteriograph along with cardiovascular markers (soluble fms-like kinase 1/placental-like growth factor, N-terminal pro-B type natriuretic peptide) in women with HDP under antihypertensive therapy, including a follow-up at 3 months and 1 year post partum, will be conducted over a 50-month period in Vienna. A prospective, longitudinal study of cardiovascular surrogate markers conducted in Oslo will serve as a comparative cohort for the Vienna cohort of haemodynamic parameters in pregnancy including a longer follow-up period of up to 3 years post partum. Each site will provide a dataset of a patient group and a control group and will be assessed for the outcome categories USCOM 1A measurements, Arteriograph measurements and Angiogenic marker measurements. To estimate the effect of antihypertensive therapy on outcome parameters, ORs with 95% CIs will be computed. Longitudinal changes of outcome parameters will be compared between normotensive and hypertensive pregnancies using mixed-effects models. ETHICS AND DISSEMINATION: Ethical approval has been granted to all participating centres. Results will be published in international peer-reviewed journals and will be presented at national and international conferences.

Generation of extracellular fluids from first-trimester decidual tissues and their validation by detecting tissue-specific secreted proteins.

The human placenta comes in direct contact with maternal cells and blood at two interfaces. The syncytiotrophoblast layer is surrounded by maternal blood at the intervillous space, and extravillous trophoblasts breach the vascular endothelial cells layer upon spiral artery remodeling and invasion of decidual veins. However, little knowledge exists about EVT-derived secreted factors, which may serve as predictive markers for obstetrical syndromes or shape the local environment at the maternal-fetal interface. Here, we define secreted EVT-associated genes and describe a method that yields interstitial fluids from patient-matched first-trimester decidua basalis and parietalis tissues.

The Influence of Pichia kluyveri Addition on the Aroma Profile of a Kombucha Tea Fermentation.

Traditional kombucha is a functional tea-based drink that has gained attention as a low or non-alcoholic beverage. The fermentation is conducted by a community of different microorganisms, collectively called SCOBY (Symbiotic Culture of Bacteria and Yeast) and typically consists of different acetic acid bacteria and fermenting yeast, and in some cases lactic acid bacteria that would convert the sugars into organic acids-mostly acetic acid. In this study, the effect of including a Pichia kluyveri starter culture in a kombucha fermentation was investigated. P. kluyveri additions led to a quicker accumulation of acetic acid along with the production of several acetate esters including isoamyl acetate and 2-phenethyl acetate. A subsequent tasting also noted a significant increase in the fruitiness of the kombucha. The significant contribution to the aroma content shows the promise of this yeast in future microbial formulations for kombucha fermentations.

Biomimetic chlorine-induced polyene cyclizations harnessing hypervalent chloroiodane-HFIP assemblies.

While bromo- and iodocyclizations have recently been successfully implemented, the challenging chlorocyclizations have been scantly investigated. We present a selective and generally applicable concept of chlorination-induced polyene cyclization by utilizing HFIP-chloroiodane networks mimicking terpene cyclases. A manifold of different alkenes was converted with excellent selectivities (up to d.r. >95 : 5). The cyclization platform was even extended to several structurally challenging terpenes and terpenoid carbon frameworks.

Longitudinal Assessment of Serum 25-Hydroxyvitamin D Levels during Pregnancy and Postpartum-Are the Current Recommendations for Supplementation Sufficient?

(1) Background: Pregnant women are at risk of vitamin D deficiency. Data on pregnancy outcomes in women with vitamin D deficiency during pregnancy are controversial, and prospective longitudinal data on vitamin D deficiency with consistent definitions in pregnant women are scarce. (2) Methods: The aim of this prospective longitudinal cohort study was to investigate 25-hydroxyvitamin D levels over the course of pregnancy and postpartum in singleton and twin pregnancies with regard to dietary and supplemental vitamin D intake and environmental factors influencing vitamin D levels, evaluated by a standardized food frequency questionnaire. (3) Results: We included 198 healthy singleton and 51 twin pregnancies for analysis. A total of 967 study visits were performed over a 3-year period. Overall, 59.5% of pregnant women were classified as vitamin D deficient in the first trimester, 54.8% in the second trimester, 58.5% in the third trimester, 66.9% at birth, and 60% 12 weeks postpartum, even though 66.4% of the study population reported daily pregnancy vitamin intake containing vitamin D. Dietary vitamin D intake did not affect vitamin D levels significantly. (4) Conclusions: The majority of pregnant women evaluated in this study were vitamin D deficient, despite administration of pregnancy vitamins containing vitamin D. Individualized vitamin D assessment during pregnancy should be considered to ensure adequate supplementation and prevention of hypovitaminosis D.

SARS-CoV-2 variant-related abnormalities detected by prenatal MRI: a prospective case-control study.

Background: There are known complications for fetuses after infection with SARS-CoV-2 during pregnancy. However, previous studies of SARS-CoV-2 in pregnancy have largely been limited to histopathologic studies of placentas and prenatal studies on the effects of different SARS-CoV-2 variants are scarce to date. To examine the effects of SARS-CoV-2 variants on the placenta and fetus, we investigated fetal and extra-fetal structures using prenatal MRI. Methods: For this prospective case-control study, two obstetric centers consecutively referred pregnant women for prenatal MRI after confirmed SARS-CoV-2 infection. Thirty-eight prenatal MRI examinations were included after confirmed infection with SARS-CoV-2 and matched 1:1 with 38 control cases with respect to sex, MRI field strength, and gestational age (average deviation 1.76 ± 1.65, median 1.5 days). Where available, the pathohistological examination and vaccination status of the placenta was included in the analysis. In prenatal MRI, the shape and thickness of the placenta, possible lobulation, and vascular lesions were quantified. Fetuses were scanned for organ or brain abnormalities. Findings: Of the 38 included cases after SARS-CoV-2 infection, 20/38 (52.6%) were infected with pre-Omicron variants and 18/38 (47.4%) with Omicron. Prenatal MRIs were performed on an average of 83 days (±42.9, median 80) days after the first positive PCR test. Both pre-Omicron (P = .008) and Omicron (P = .016) groups showed abnormalities in form of a globular placenta compared to control cases. In addition, placentas in the pre-Omicron group were significantly thickened (6.35, 95% CI .02-12.65, P = .048), and showed significantly more frequent lobules (P = .046), and hemorrhages (P = .002). Fetal growth restriction (FGR) was observed in 25% (n = 5/20, P = .017) in the pre-Omicron group. Interpretation: SARS-CoV-2 infections in pregnancy can lead to placental lesions based on vascular events, which can be well visualized on prenatal MRI. Pre-Omicron variants cause greater damage than Omicron sub-lineages in this regard. Funding: Vienna Science and Technology Fund.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women.

BACKGROUND: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events. OBJECTIVE: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection. STUDY DESIGN: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. RESULTS: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation. CONCLUSION: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

Awareness of obstetricians for long-term risks in women with a history of preeclampsia or HELLP syndrome.

PURPOSE: Hypertensive disorders of pregnancy are still a leading cause of maternal and neonatal morbidity and mortality worldwide. Women with a history of preeclampsia have an increased risk for future cardiovascular and cerebrovascular disease, renal disease as well as diabetes mellitus. There is little knowledge on postpartum risk management. The aim of this study was to assess follow-up care for patients after pre-eclampsia or HELLP syndrome. METHODS: This questionnaire-based cross-sectional study aimed to evaluate the current recommendations of obstetricians in Austria regarding follow-up care, long-term risk counselling and risk of recurrence in future pregnancies after preeclampsia or HELLP syndrome. Data were collected using a survey, based on recommendations given by three substantial guidelines on hypertensive disorders of pregnancy, which was distributed via e-mail to 69 public obstetric departments in Austria. Each obstetric department was required to answer one questionnaire per local protocol. RESULTS: Our results revealed that of the 48 participating hospitals most obstetricians are aware of the importance of follow-up care for women after a pregnancy complicated by preeclampsia. Our data show that most physicians counselled patients about the future cardiovascular health risks associated with preeclampsia or HELLP syndrome (79.2%). Most obstetricians recommended lifestyle modification (77.1%) and continued blood pressure measurements (97.9%). All centers stated to counsel about the risk of recurrence (100%). However, counselling regarding follow-up care to exclude kidney damage (37.5%) and underlying diseases like thrombophilia (39.6%) were less prioritized. CONCLUSIONS: We were able to show that counselling concerning the risk of long-term cardiovascular disease and risk of recurrence after a pregnancy complicated by preeclampsia or HELLP syndrome has been established in obstetric departments in public hospitals. Regarding the evaluation of underlying chronic diseases such as thrombophilia or renal disease, as well as counselling on the future risk of renal disease is still improvable according to our data. Further evaluation of follow-up care after hypertensive disorders of pregnancy in the outpatient and private sector and implementation of structured guidelines for follow-up, as well as screening for cardiovascular disease are necessary to ensure adequate risk management and to provide opportunities for prevention.

Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension.

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty-seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt-1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P<0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P<0.001 for both) compared with women who delivered for other reasons. SFlt-1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications (P<0.05). Half of women with angiogenic imbalance (sFlt-1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0-2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.