304 results on '"Magnus Westgren"'
Search Results
2. Long-term neurodevelopmental outcome in children born after vacuum-assisted delivery compared with second-stage caesarean delivery and spontaneous vaginal delivery: a cohort study
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Magnus Westgren, Katarina Lindström, Stefhanie Romero, Johanna Listermar, and Gunilla Ajne
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Pediatrics ,RJ1-570 - Abstract
Objective To evaluate long-term neurodevelopment in children born after low-or mid-station vacuum-assisted delivery (VAD) compared with children delivered by second-stage caesarean delivery (SSCD) or spontaneous vaginal delivery (SVD).Design Cross-sectional cohort study.Setting Two delivery wards, Karolinska University Hospital, Sweden.Patients 253 children born by low-station or mid-station VAD, 247 children born after an SVD, and 86 children born via an SSCD accepted to participate.Interventions The Five-to-Fifteen questionnaire was used as a validated screening method for neurodevelopmental difficulties, assessed by parents.Main outcomes measures Results in the Five-to-Fifteen questionnaire. In addition, registered neurodevelopmental ICD-10 diagnoses were collected. Regression analyses estimated associations between delivery modes.Results Children born after VAD exhibited an increased rate of long-term neurodevelopmental difficulties in motor skills (OR 2.2, 95% CI 1.3 to 3.8) and perception (OR 1.7, 95% CI 1.002 to 2.9) compared with SVD. Similar findings were seen in the group delivered with an SSCD compared with SVD (motor skills: OR 3.3, 95% CI 1.8 to 6.4 and perception: OR 2.3, 95% CI 1.2 to 4.4). The increased odds for motor skills difficulties after VAD and SSCD remained after adjusting for proposed confounding variables. There were significantly more children in the VAD group with registered neurodevelopmental ICD-10 diagnoses such as attention deficit/hyperactivity disorders.Conclusions The differences in long-term neurodevelopmental difficulties in children delivered with a VAD or SSCD compared with SVD in this study indicate the need for increased knowledge in the field to optimise the management of second stage of labour.
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- 2023
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3. Perinatal outcome after vacuum assisted delivery with digital feedback on traction force; a randomised controlled study
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Stefhanie Romero, Kristina Pettersson, Khurram Yousaf, Magnus Westgren, and Gunilla Ajne
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Vacuum assisted delivery ,Traction force ,Haptic feedback ,Neonatal outcome ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background Low and mid station vacuum assisted deliveries (VAD) are delicate manual procedures that entail a high degree of subjectivity from the operator and are associated with adverse neonatal outcome. Little has been done to improve the procedure, including the technical development, traction force and the possibility of objective documentation. We aimed to explore if a digital handle with instant haptic feedback on traction force would reduce the neonatal risk during low or mid station VAD. Methods A two centre, randomised superiority trial at Karolinska University Hospital, Sweden, 2016–2018. Cases were randomised bedside to either a conventional or a digital handle attached to a Bird metal cup (50 mm, 80 kPa). The digital handle measured applied force including an instant notification by vibration when high levels of traction force were predicted according to a predefined algorithm. Primary outcome was a composite of hypoxic ischaemic encephalopathy, intracranial haemorrhage, seizures, death and/or subgaleal hematoma. Three hundred eighty low and mid VAD in each group were estimated to decrease primary outcome from six to 2 %. Results After 2 years, an interim analyse was undertaken. Meeting the inclusion criteria, 567 vacuum extractions were randomized to the use of a digital handle (n = 296) or a conventional handle (n = 271). Primary outcome did not differ between the two groups: (2.7% digital handle vs 2.6% conventional handle). The incidence of primary outcome differed significantly between the two delivery wards (4% vs 0.9%, p
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- 2021
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4. Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings
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Lotta Herling, Jonas Johnson, Kjerstin Ferm-Widlund, Fredrik Bergholm, Peter Lindgren, Sven-Erik Sonesson, Ganesh Acharya, and Magnus Westgren
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Fetal cardiac function ,Tissue Doppler imaging ,Automated analysis ,Intrauterine transfusion ,Fetal anemia ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Fetal anemia is associated with a hyperdynamic circulation and cardiac remodeling. Rapid intrauterine transfusion (IUT) of blood with high hematocrit and viscosity into the umbilical vein used to treat this condition can temporarily further affect fetal heart function. The aim of this study was to evaluate the short-term changes in fetal myocardial function caused by IUT using automated analysis of cine-loops of the fetal heart obtained by color tissue Doppler imaging (cTDI). Methods Fetal echocardiography was performed before and after IUT. cTDI recordings were obtained in a four-chamber view and regions of interest were placed at the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls. Myocardial velocities were analyzed by an automated analysis software to obtain peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm), rapid ventricular filling (Em) and Em/Am ratio was calculated. Myocardial velocities were converted to z-scores using published reference ranges. Delta z-scores (after minus before IUT) were calculated. Correlations were assessed between variables and hemoglobin before IUT. Results Thirty-two fetuses underwent 70 IUTs. Fourteen were first time transfusions. In the LV and septal walls, all myocardial velocities were significantly increased compared to normal values, whereas in the RV only Sm was increased before IUT (z-scores 0.26–0.52). In first time IUTs, there was a negative correlation between LV Em (rho = − 0.61, p = 0.036) and LV Em/Am (rho = − 0.82, p = 0.001) z-scores and hemoglobin before IUT. The peak myocardial velocities that were increased before IUT decreased, whereas LV Em/Am increased significantly after IUT. Conclusions This study showed that peak myocardial velocities assessed by cTDI are increased in fetuses before IUT reflecting the physiology of hyperdynamic circulation. In these fetuses, the fetal heart is able to adapt and efficiently handle the volume load caused by IUT by altering its myocardial function.
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- 2020
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5. Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies
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Åsa Ekblad‐Nordberg, Lilian Walther‐Jallow, Magnus Westgren, and Cecilia Götherström
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cell therapy ,inherited diseases ,prenatal ,stem cell ,treatment strategies ,Medicine (General) ,R5-920 ,Cytology ,QH573-671 - Abstract
Abstract Imagine the profits in quality of life that can be made by treating inherited diseases early in life, maybe even before birth! Immense cost savings can also be made by treating diseases promptly. Hence, prenatal stem cell therapy holds great promise for developing new and early‐stage treatment strategies for several diseases. Successful prenatal stem cell therapy would represent a major step forward in the management of patients with hematological, metabolic, or immunological disorders. However, treatment before birth has several limitations, including ethical issues. In this review, we summarize the past, the present, and the future of prenatal stem cell therapy, which includes an overview of different stem cell types, preclinical studies, and clinical attempts treating various diseases. We also discuss the current challenges and future strategies for prenatal stem cell therapy and also new approaches, which may lead to advancement in the management of patients with severe incurable diseases.
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- 2020
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6. Incidence and risk factors of transfusion reactions in postpartum blood transfusions
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Lars Thurn, Agneta Wikman, Magnus Westgren, and Pelle G. Lindqvist
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Specialties of internal medicine ,RC581-951 - Abstract
Abstract: Postpartum hemorrhages with blood transfusions are increasing in many high-resource countries. Currently, up to 3% of all women receive blood transfusion postpartum. Most blood transfusions are safe and, in many cases, are lifesaving, but there are significant concerns about adverse reactions. Pregnancy is associated with higher levels of leukocyte antibodies and has a modulating effect on the immune system. Our objective was to investigate whether blood transfusions postpartum are accompanied by an increased risk for transfusion reactions (TRs) compared with transfusions given to nonpregnant women. We included all women who gave birth in Stockholm County, Sweden between 1990 and 2011. Data from the Swedish National Birth Registry were linked to the Stockholm Transfusion Database and included information on blood components administered and whether a TR occurred in women who received blood transfusions postpartum. Background controls were nonpregnant women who received blood transfusions during the study period. The study cohort consisted of 517 854 women. Of these, 12 183 (2.4%) received a blood transfusion. We identified 96 events involving a TR postpartum, giving a prevalence of 79 per 10 000 compared with 40 per 10 000 among nonpregnant women (odds ratio, 2.0; 95% confidence interval, 1.6-2.5). Preeclampsia was the single most important risk factor for TRs (odds ratio, 2.1; 95% confidence interval, 1.7-2.6). We conclude that special care should be taken when women with preeclampsia are considered for blood transfusion postpartum, because our findings indicate that pregnancy is associated with an increased risk for TRs.
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- 2019
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7. Effect of team training and monitoring on the rate of failed mid and low cavity vacuum extraction: a hospital based intervention study
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Kristina Pettersson, Magnus Westgren, Rebecca Götze-Eriksson, and Gunilla Ajne
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Vacuum extraction ,Failed extraction ,Team training ,Hawthorne effect ,Monitoring ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Background Clinical team training has been advocated as a means to improve delivery care, and failed extractions is a suggested variable for clinical audit in instrumental vaginal delivery. Other activities may also have intended or unintended effects on care processes or outcomes. Methods We retrospectively observed 1074 mid and low vacuum extraction deliveries during three time periods (prevalence periods): Baseline (period 0), implemented team training (period 1 and 2) and monitoring of traction force during vacuum extraction (period 2). Our primary outcome was failed extraction followed by emergency cesarean section or obstetric forceps delivery. Results The prevalence proportion (relative risk) of failed extraction decreased significantly after implementation of team training, from 19% (period 0) to 8 % (period 1), corresponding to a relative risk of 0.48 [0.26–0.87]. The secondary procedural outcome complicated delivery (duration > 15 min or number of pulls > 6, or cup detachment > 1) was decreased in period 2 compared to period 1, RR 0.42 [0.23–0.76]. Secondary clinical (neonatal) outcome were not affected. Conclusion Clinically based educational efforts and increased monitoring improved procedural outcome without improving neonatal outcome. The study design has inherent limitations in making causal inference.
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- 2019
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8. Maternal obesity and stillbirth at term; placental pathology-A case control study.
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Hanna Åmark, Magnus Westgren, Meeli Sirotkina, Ingela Hulthén Varli, Martina Persson, and Nikos Papadogiannakis
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Medicine ,Science - Abstract
ObjectiveThe aim was to explore the potential role of the placenta for the risk of stillbirth at term in pregnancies of obese women.MethodsThis was a case-control study comparing placental findings from term stillbirths with placental findings from live born infants. Cases were singleton term stillbirths to normal weight or obese women, identified in the Stockholm stillbirth database, n = 264 and n = 87, respectively. Controls were term singletons born alive to normal weight or obese women, delivered between 2002-2005 and between 2018-2019. Placentas were compared between women with stillborn and live-born infants, using logistic regression analyses.ResultsA long and hyper coiled cord, cord thrombosis and velamentous cord insertion were stronger risk factors for stillbirth in obese women compared to normal weight women. When these variables were adjusted for in the logistic regression analysis, also adjusted for potential confounders, the odds ratio for stillbirth in obese women decreased from 1.89 (CI 1.24-2.89) to 1.63 (CI 1.04-2.56).ConclusionApproximately one fourth of the effect of obesity on the risk of stillbirth in term pregnancies is explained by umbilical cord associated pathology.
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- 2021
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9. Cellular Subsets of Maternal Microchimerism in Umbilical Cord Blood
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Anna Maria Jonsson Kanold, Magnus Westgren, and Cecilia Götherström
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Medicine - Abstract
Maternal microchimerism may arise in the offspring during pregnancy, and may be favorable or unfavorable. Additionally, maternal cells present in umbilical cord blood used for stem cell transplantation may affect the outcome after transplantation. The aim of this study was to evaluate the cellular subset and frequency of maternal cells in umbilical cord blood following vaginal deliveries and elective Cesarean sections where the umbilical cord clamping time was measured. A total of 44 healthy women with normal pregnancies were included in the study. Of these, 24 delivered vaginally and 20 by elective Cesarean sections. In the fresh umbilical cord blood, cellular subsets of CD3+ (T-cells), CD19+ (B-cells), CD33+ (myeloid cells), CD34+ (hematopoietic progenitor cells) and CD56+ (natural killer cells) cells were isolated and DNA extracted. A single-nucleotide polymorphism unique to the mother was identified and maternal microchimerism in the different cellular fractions was detected using quantitative real-time polymerase chain reaction with a sensitivity of 0.01%. Overall, 5 out of the 44 (11%) umbilical cord blood samples contained maternal microchimerism. The positive fractions were total DNA (whole blood, n = 3), CD34+ ( n = 1), CD56+ ( n = 1) and CD34+/CD56+ ( n = 1). Overall, four of the five (80%) positive samples were from Cesarean sections and one was from a vaginal delivery. The conclusion from this study is that maternal microchimerism in umbilical cord blood is not a common phenomenon but includes both lymphoid and hematopoietic progenitor lineages.
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- 2019
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10. In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
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Maria Pernemalm, AnnSofi Sandberg, Yafeng Zhu, Jorrit Boekel, Davide Tamburro, Jochen M Schwenk, Albin Björk, Marie Wahren-Herlenius, Hanna Åmark, Claes-Göran Östenson, Magnus Westgren, and Janne Lehtiö
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proteogenomics ,plasma ,proteomics ,mass spectrometry ,biomarker discovery ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Here, we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis, we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy.
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- 2019
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11. Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells
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Agneta Månsson-Broberg, Sergey Rodin, Ivana Bulatovic, Cristián Ibarra, Marie Löfling, Rami Genead, Eva Wärdell, Ulrika Felldin, Carl Granath, Evren Alici, Katarina Le Blanc, C.I. Edvard Smith, Alena Salašová, Magnus Westgren, Erik Sundström, Per Uhlén, Ernest Arenas, Christer Sylvén, Karl Tryggvason, Matthias Corbascio, Oscar E. Simonson, Cecilia Österholm, and Karl-Henrik Grinnemo
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs) has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN)-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.
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- 2016
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12. Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis
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Arjang Baygan, Wictor Aronsson-Kurttila, Gianluca Moretti, Babylonia Tibert, Göran Dahllöf, Lena Klingspor, Britt Gustafsson, Bita Khoein, Guido Moll, Charlotta Hausmann, Britt-Marie Svahn, Magnus Westgren, Mats Remberger, Behnam Sadeghi, and Olle Ringden
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graft-versus-host disease ,mesenchymal stromal cells ,hematopoietic stem cell transplantation ,hemorrhagic cystitis ,decidual stromal cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9–2.9) × 106 DSCs/kg. The patients were given 2 (1–5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy.
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- 2017
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13. Predictive value of traction force measurement in vacuum extraction: Development of a multivariate prognostic model.
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Kristina Pettersson, Khurram Yousaf, Jonas Ranstam, Magnus Westgren, and Gunilla Ajne
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Medicine ,Science - Abstract
To enable early prediction of strong traction force vacuum extraction.Observational cohort.Karolinska University Hospital delivery ward, tertiary unit.Term mid and low metal cup vacuum extraction deliveries June 2012-February 2015, n = 277.Traction forces during vacuum extraction were collected prospectively using an intelligent handle. Levels of traction force were analysed pairwise by subjective category strong versus non-strong extraction, in order to define an objective predictive value for strong extraction.A logistic regression model based on the shrinkage and selection method lasso was used to identify the predictive capacity of the different traction force variables.Total (time force integral, Newton minutes) and peak traction (Newton) force in the first to third pull; difference in traction force between the second and first pull, as well as the third and first pull respectively. Accumulated traction force at the second and third pull.Subjectively categorized extraction as strong versus non-strong.The prevalence of strong extraction was 26%. Prediction including the first and second pull: AUC 0,85 (CI 0,80-0,90); specificity 0,76; sensitivity 0,87; PPV 0,56; NPV 0,94. Prediction including the first to third pull: AUC 0,86 (CI 0,80-0,91); specificity 0,87; sensitivity 0,70; PPV 0,65; NPV 0,89.Traction force measurement during vacuum extraction can help exclude strong category extraction from the second pull. From the third pull, two-thirds of strong extractions can be predicted.
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- 2017
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14. Clinical Outcome in Singleton and Multiple Pregnancies with Placental Chorangioma.
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Meeli Sirotkina, Konstantinos Douroudis, Nikos Papadogiannakis, and Magnus Westgren
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Medicine ,Science - Abstract
Chorangiomas (CAs) are the most common non-trophoblastic tumor-like-lesions of the placenta. Although the clinical significance of small CAs is unknown, the large lesions are often associated with maternal and fetal complications. The aim of our study was to assess the maternal clinical characteristics and neonatal outcome in singleton and multiple pregnancies with placental CA.Among 15742 selected placentas 170 CAs were diagnosed. Pregnancy and neonatal outcomes were analyzed in singleton (n = 121) and multiple (n = 49) pregnancy groups including 121 and 100 neonates, respectively.The frequency of APGAR score
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- 2016
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15. A research study of the association between maternal microchimerism and systemic lupus erythematosus in adults: a comparison between patients and healthy controls based on single-nucleotide polymorphism using quantitative real-time PCR.
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Anna Maria Jonsson Kanold, Elisabet Svenungsson, Iva Gunnarsson, Cecilia Götherström, Leonid Padyukov, Nikos Papadogiannakis, Mehmet Uzunel, and Magnus Westgren
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Medicine ,Science - Abstract
BackgroundNaturally acquired microchimerism may arise in the mother and her child during pregnancy when bidirectional trafficking of cells occurs through the placental barrier. The occurrence of maternal microchimerism (maternal cells in the offspring) has been associated with several autoimmune diseases, especially in children. Systemic Lupus erythematosus (SLE) is an autoimmune disorder with a resemblance to graft-versus-host disease. The aim of this study was to investigate the association between maternal microchimerism in the blood and SLE.Methodology/principal findingsThirty-two patients with SLE, 17 healthy brothers of the patients, and an additional 12 unrelated healthy men were the subjects in this study. A single-nucleotide polymorphism unique to each mother was identified, and maternal microchimerism in the study group and in the control group was detected using a quantitative real-time polymerase chain reaction technique. No differences in the frequency or the concentration of maternal cells were apparent in the blood of patients with SLE or in that of the controls. Two patients and one control tested positive for maternal microchimerism, but the positive subjects were all negative at a follow-up 16 years later. The sensitivity of the method was estimated to 1/10.000.Conclusions/significanceThese results show no association between SLE and maternal microchimerism. The frequency of maternal microchimerism in the blood of adults overall may be lower than earlier reported.
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- 2013
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16. Targeted routine antenatal anti-D prophylaxis in the prevention of RhD immunisation--outcome of a new antenatal screening and prevention program.
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Eleonor Tiblad, Agneta Taune Wikman, Gunilla Ajne, Agneta Blanck, Yvonne Jansson, Anita Karlsson, Elisabeth Nordlander, Bibi Shassti Holländer, and Magnus Westgren
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Medicine ,Science - Abstract
OBJECTIVE: To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP). MATERIALS AND METHODS: We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250-300 µg) was administered intramuscularly in gestational week 28-30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy. RESULTS: During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15-0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500. CONCLUSIONS: Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.
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- 2013
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17. Traction force profile in children with severe perinatal outcomes delivered with a digital vacuum extraction handle: A case–control study
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Stefhanie Romero, Kristina Pettersson, Khurram Yousaf, Magnus Westgren, and Gunilla Ajne
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Vacuum Extraction, Obstetrical ,Pregnancy ,Cesarean Section ,Traction ,Case-Control Studies ,Infant, Newborn ,Humans ,Obstetrics and Gynecology ,Female ,General Medicine ,Child ,Delivery, Obstetric ,Retrospective Studies - Abstract
During the second stage of labor, vacuum-assisted delivery is an alternative to forceps delivery and emergency cesarean section. Extensive research concerning perinatal outcomes has indicated that the risk of complications, although rare, is higher than with a spontaneous vaginal delivery. An important factor related to perinatal outcomes is the traction force applied. Our research group previously developed a digital extraction handle, the Vacuum Intelligent Handle-3 (VIH3), that measures and records traction force. The objective of this study was to compare traction force profiles in children with and without severe perinatal outcomes delivered with the digital handle. A secondary aim was to establish a safe force limit.This was an observational case-control study at the delivery ward at Karolinska University Hospital, Sweden. In total, 573 children delivered with the digital handle between 2012 and 2018 were included. Cases were defined as a composite of severe perinatal outcomes, including subgaleal hematoma, intracranial hemorrhage, hypoxic ischemic encephalopathy 1-3, seizures or death. The cases in the cohort were matched 1:3 based on five matching variables. Traction profiles were analyzed using the MATLAB® software and conditional logistic regression.The incidence of severe perinatal outcomes was 2.3%. The 13 cases were matched with three controls each (n = 39). A statistically significant increased odds for higher total traction forces was seen in the case group (odds ratio [OR] 1.004; 95% confidence interval [CI] 1.001-1.007) and for the peak force (OR 1.022; 95% CI 1.004-1.041). Several procedure-related parameters were significantly increased in the case group. As expected, some neonatal characteristics also differed significantly. An upper force limit of 343 Newton minutes (Nmin) revealed an 86% reduction in severe perinatal outcomes (adjusted OR 0.14; 95% CI 0.04-0.5).Children with severe perinatal outcomes had traction force profiles with significantly higher forces. The odds for severe perinatal outcomes increased for every increase in Nmin and Newton used during the extraction procedure. A calculated total force level of 343 Nmin is suggested as an upper safety limit, but this must be tested prospectively to provide validity.
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- 2022
18. Mesenchymal Stem Cell Therapy for Osteogenesis Imperfecta
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Anna L. David, Eva Åström, Cecilia Götherström, Magnus Westgren, and Lilian Walther-Jallow
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Oncology ,medicine.medical_specialty ,business.industry ,Mesenchymal stem cell ,Obstetrics and Gynecology ,Cell Differentiation ,Mesenchymal Stem Cells ,Osteogenesis Imperfecta ,Mesenchymal Stem Cell Transplantation ,medicine.disease ,Clinical trial ,Transplantation ,Safety profile ,Clinical therapy ,Paracrine signalling ,Fetus ,Osteogenesis imperfecta ,Internal medicine ,Bone cell ,Animals ,Humans ,Medicine ,business - Abstract
The aim of this study was to provide a brief overview on the background and rationale on treating fetuses and children suffering from osteogenesis imperfecta (OI) with mesenchymal stem cells (MSCs). MSCs ability to migrate, engraft, and differentiate into bone cells and to act via paracrine effects on the recipient's tissues makes these cells promising candidates as a clinical therapy for OI. Animal work and limited clinical studies in humans support the use of MSC in treating OI. Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic profile and thereby may enable this potential therapy to become widely available. MSC transplantation before and after birth to treat OI is an experimental therapy that is currently tested in the international multicentre phase I/II clinical trial BOOSTB4 that aims to assess the safety and efficacy of fetal MSC transplantation for the treatment of severe types of OI.
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- 2021
19. Perinatal outcome after vacuum assisted delivery with digital feedback on traction force; a randomised controlled study
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Gunilla Ajne, Khurram Yousaf, Stefhanie Romero, Kristina Pettersson, and Magnus Westgren
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Adult ,medicine.medical_specialty ,Vacuum Extraction, Obstetrical ,Vacuum assisted delivery ,Digital feedback ,Vacuum assisted ,Perinatal outcome ,Outcome (game theory) ,lcsh:Gynecology and obstetrics ,03 medical and health sciences ,0302 clinical medicine ,Superiority Trial ,Pregnancy ,Birth Injuries ,medicine ,Humans ,030212 general & internal medicine ,lcsh:RG1-991 ,030219 obstetrics & reproductive medicine ,business.industry ,Incidence (epidemiology) ,Infant, Newborn ,Pregnancy Outcome ,Obstetrics and Gynecology ,Neonatal outcome ,University hospital ,Traction force ,Treatment Outcome ,Cohort ,Hypoxia-Ischemia, Brain ,Physical therapy ,Female ,business ,Haptic feedback ,Intracranial Hemorrhages ,Research Article - Abstract
Background Low and mid station vacuum assisted deliveries (VAD) are delicate manual procedures that entail a high degree of subjectivity from the operator and are associated with adverse neonatal outcome. Little has been done to improve the procedure, including the technical development, traction force and the possibility of objective documentation. We aimed to explore if a digital handle with instant haptic feedback on traction force would reduce the neonatal risk during low or mid station VAD. Methods A two centre, randomised superiority trial at Karolinska University Hospital, Sweden, 2016–2018. Cases were randomised bedside to either a conventional or a digital handle attached to a Bird metal cup (50 mm, 80 kPa). The digital handle measured applied force including an instant notification by vibration when high levels of traction force were predicted according to a predefined algorithm. Primary outcome was a composite of hypoxic ischaemic encephalopathy, intracranial haemorrhage, seizures, death and/or subgaleal hematoma. Three hundred eighty low and mid VAD in each group were estimated to decrease primary outcome from six to 2 %. Results After 2 years, an interim analyse was undertaken. Meeting the inclusion criteria, 567 vacuum extractions were randomized to the use of a digital handle (n = 296) or a conventional handle (n = 271). Primary outcome did not differ between the two groups: (2.7% digital handle vs 2.6% conventional handle). The incidence of primary outcome differed significantly between the two delivery wards (4% vs 0.9%, p Conclusions The incidence of primary outcome was lower than estimated and the study was underpowered. However, the difference between the two delivery wards might reflect varying degree of experience of the technical equipment. An objective documentation of the extraction procedure is an attractive alternative in respect to safety and clinical training. To demonstrate improved safety, a multicentre study is required to reach an adequate cohort. This was beyond the scope of the study. Trial registration ClinicalTrials.gov NCT03071783, March 1, 2017, retrospectively registered.
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- 2021
20. Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings
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K. Ferm-Widlund, Peter Lindgren, Fredrik Bergholm, Lotta Herling, Ganesh Acharya, Magnus Westgren, Jonas Johnson, and Sven-Erik Sonesson
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Cardiac function curve ,Adult ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Blood Transfusion, Intrauterine ,030204 cardiovascular system & hematology ,Doppler imaging ,Umbilical vein ,Ultrasonography, Prenatal ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Tissue Doppler imaging ,0302 clinical medicine ,Fetal Heart ,Pregnancy ,Fetal cardiac function ,Internal medicine ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Ultrasonography, Doppler, Color ,Angiology ,Fetus ,medicine.diagnostic_test ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750 ,business.industry ,Research ,Ultrasound ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750 ,Anemia ,Fetal anemia ,General Medicine ,Automated analysis ,Intrauterine transfusion ,lcsh:RC666-701 ,Hyperdynamic circulation ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Fetal echocardiography - Abstract
Background Fetal anemia is associated with a hyperdynamic circulation and cardiac remodeling. Rapid intrauterine transfusion (IUT) of blood with high hematocrit and viscosity into the umbilical vein used to treat this condition can temporarily further affect fetal heart function. The aim of this study was to evaluate the short-term changes in fetal myocardial function caused by IUT using automated analysis of cine-loops of the fetal heart obtained by color tissue Doppler imaging (cTDI). Methods Fetal echocardiography was performed before and after IUT. cTDI recordings were obtained in a four-chamber view and regions of interest were placed at the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls. Myocardial velocities were analyzed by an automated analysis software to obtain peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm), rapid ventricular filling (Em) and Em/Am ratio was calculated. Myocardial velocities were converted to z-scores using published reference ranges. Delta z-scores (after minus before IUT) were calculated. Correlations were assessed between variables and hemoglobin before IUT. Results Thirty-two fetuses underwent 70 IUTs. Fourteen were first time transfusions. In the LV and septal walls, all myocardial velocities were significantly increased compared to normal values, whereas in the RV only Sm was increased before IUT (z-scores 0.26–0.52). In first time IUTs, there was a negative correlation between LV Em (rho = − 0.61, p = 0.036) and LV Em/Am (rho = − 0.82, p = 0.001) z-scores and hemoglobin before IUT. The peak myocardial velocities that were increased before IUT decreased, whereas LV Em/Am increased significantly after IUT. Conclusions This study showed that peak myocardial velocities assessed by cTDI are increased in fetuses before IUT reflecting the physiology of hyperdynamic circulation. In these fetuses, the fetal heart is able to adapt and efficiently handle the volume load caused by IUT by altering its myocardial function.
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- 2020
21. A new microdialysis probe for continuous lactate measurement during fetal monitoring
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Paul P. van den Berg, Henk Groen, Froukje Tigchelaar, Magnus Westgren, Kirsten D. Huinink, Thomas I. F. H. Cremers, Value, Affordability and Sustainability (VALUE), Reproductive Origins of Adult Health and Disease (ROAHD), Analytical Biochemistry, Medicinal Chemistry and Bioanalysis (MCB), and Pharmaceutical Analysis
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Microdialysis ,03 medical and health sciences ,Subcutaneous Tissue ,0302 clinical medicine ,Pregnancy ,In vivo ,Animals ,Medicine ,Cardiotocography ,Original Research Article ,Oximetry ,030212 general & internal medicine ,Rats, Wistar ,LABOR ,Acidosis ,Oxygen saturation (medicine) ,Investigation ,lactate ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,fetal monitoring ,Albumin ,Obstetrics and Gynecology ,Membranes, Artificial ,General Medicine ,Oxygenation ,Cannula ,fetal scalp electrode ,DIABETIC-PATIENTS ,Fetal Diseases ,CLINICAL CEREBRAL MICRODIALYSIS ,Anesthesia ,Models, Animal ,Lactates ,Female ,prenatal care ,medicine.symptom ,delivery ,fetal acidosis ,business ,cardiotocography ,cesarean ,SKIN - Abstract
Introduction Cardiotocography (CTG) is currently the most commonly used method for intrapartum fetal monitoring during labor. However, a high false-positive rate of fetal acidosis indicated by CTG leads to an increase in obstetric interventions. We developed a microdialysis probe that is integrated into a fetal scalp electrode allowing continuous measurement of lactate subcutaneously, thus giving instant information about the oxygenation status of the fetus. Our aim was to establish proof of concept in an animal model using a microdialysis probe to monitor lactate subcutaneously.Material and methods We performed an in vivo study in adult male wild-type Wistar rats. We modified electrodes used for CTG monitoring in human fetuses to incorporate a microdialysis membrane. Optimum flow rates for microdialysis were determined in vitro. For the in vivo experiment, a microdialysis probe was inserted into the skin on the back of the animal. De-oxygenation and acidosis were induced by lowering the inspiratory oxygen pressure. Oxygenation and heart rate were monitored. A jugular vein cannula was inserted to draw blood samples for analysis of lactate, pH, pco(2), and saturation. Lactate levels in dialysate were compared with plasma lactate levels.Results Baseline blood lactate levels were around 1 mmol/L. Upon de-oxygenation, oxygen saturation fell to below 40% for 1 h and blood lactate levels increased 2.5-fold. Correlation of dialysate lactate levels with plasma lactate levels was 0.89 resulting in an R-2 of .78 in the corresponding linear regression.Conclusions In this animal model, lactate levels in subcutaneous fluid collected by microdialysis closely reflected blood lactate levels upon transient de-oxygenation, indicating that our device is suitable for subcutaneous measurement of lactate. Microdialysis probe technology allows the measurement of multiple compounds in the dialysate, such as glucose, albumin, or inflammatory mediators, so this technique may offer the unique possibility to shed light on fetal physiology during the intrapartum period.
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- 2020
22. Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology
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Francesc Figueras, Kurt Hecher, Eduard Gratacós, Alan W. Flake, Kathleen J. Beach, Gillian Yaz, Mehali Patel, Anna L. David, Helena M. Gardiner, Karel Marsal, Albert Batista, Christoph Lees, James Power, Steve Thornton, Anke Diemert, Jan Deprest, Rebecca Spencer, Helen Turier, Neil Marlow, Magnus Westgren, Gill Norman, Donald Peebles, Beverley Power, Fatima Crispi, Marcy Powell, and Jana Brodszki
- Subjects
medicine.medical_specialty ,MedDRA ,POSTPARTUM HEMORRHAGE ,Psychological intervention ,INCLUSION ,GUIDELINES ,DIAGNOSIS ,CLASSIFICATION ,Terminology ,Fetus ,Terminology as Topic ,Humans ,Medicine ,Obstetrics & Reproductive Medicine ,Grading (education) ,Intensive care medicine ,Adverse effect ,Genetics (clinical) ,Genetics & Heredity ,Pregnancy ,Science & Technology ,HYPERTENSION ,business.industry ,Obstetrics & Gynecology ,Obstetrics and Gynecology ,1103 Clinical Sciences ,Reference Standards ,medicine.disease ,PREVENTION ,IRON-DEFICIENCY ,Pregnancy Complications ,Clinical trial ,PREGNANCY ,1114 Paediatrics and Reproductive Medicine ,CLINICAL MANAGEMENT ,Female ,business ,Life Sciences & Biomedicine - Abstract
OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety. ispartof: PRENATAL DIAGNOSIS vol:42 issue:1 pages:15-26 ispartof: location:England status: published
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- 2022
23. Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies
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Åsa Ekblad-Nordberg, Magnus Westgren, Cecilia Götherström, and Lilian Walther-Jallow
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0301 basic medicine ,medicine.medical_specialty ,prenatal ,Transplantation Conditioning ,medicine.medical_treatment ,Cell- and Tissue-Based Therapy ,Concise Reviews ,Cell therapy ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Pregnancy ,treatment strategies ,medicine ,Incurable diseases ,Humans ,lcsh:QH573-671 ,Intensive care medicine ,lcsh:R5-920 ,Ethical issues ,business.industry ,lcsh:Cytology ,Concise Review ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,General Medicine ,Stem-cell therapy ,3. Good health ,Cost savings ,stem cell ,030104 developmental biology ,Treatment strategy ,Female ,Stem cell ,cell therapy ,business ,lcsh:Medicine (General) ,030217 neurology & neurosurgery ,inherited diseases ,Developmental Biology ,Stem Cell Transplantation - Abstract
Imagine the profits in quality of life that can be made by treating inherited diseases early in life, maybe even before birth! Immense cost savings can also be made by treating diseases promptly. Hence, prenatal stem cell therapy holds great promise for developing new and early-stage treatment strategies for several diseases. Successful prenatal stem cell therapy would represent a major step forward in the management of patients with hematological, metabolic, or immunological disorders. However, treatment before birth has several limitations, including ethical issues. In this review, we summarize the past, the present, and the future of prenatal stem cell therapy, which includes an overview of different stem cell types, preclinical studies, and clinical attempts treating various diseases. We also discuss the current challenges and future strategies for prenatal stem cell therapy and also new approaches, which may lead to advancement in the management of patients with severe incurable diseases. Significance statement This review summarizes the past, the present progress, and the future potential of prenatal stem cell therapy. Recent and previous studies are discussed, focusing on both preclinical and clinical data, highlighting both the drawbacks and the novel findings leading to the progress of prenatal stem cell therapies into the clinic.
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- 2019
24. Incidence and risk factors of transfusion reactions in postpartum blood transfusions
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Agneta Wikman, Magnus Westgren, Lars Thurn, and Pelle G. Lindqvist
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Adult ,medicine.medical_specialty ,Blood transfusion ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Risk Assessment ,Preeclampsia ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Blood Component Transfusion ,Odds Ratio ,Humans ,Medicine ,Blood Transfusion ,Risk factor ,Pregnancy ,030219 obstetrics & reproductive medicine ,Transfusion Medicine ,business.industry ,Obstetrics ,Incidence ,Postpartum Hemorrhage ,Transfusion Reaction ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Cohort ,Female ,business ,Postpartum period - Abstract
Postpartum hemorrhages with blood transfusions are increasing in many high-resource countries. Currently, up to 3% of all women receive blood transfusion postpartum. Most blood transfusions are safe and, in many cases, are lifesaving, but there are significant concerns about adverse reactions. Pregnancy is associated with higher levels of leukocyte antibodies and has a modulating effect on the immune system. Our objective was to investigate whether blood transfusions postpartum are accompanied by an increased risk for transfusion reactions (TRs) compared with transfusions given to nonpregnant women. We included all women who gave birth in Stockholm County, Sweden between 1990 and 2011. Data from the Swedish National Birth Registry were linked to the Stockholm Transfusion Database and included information on blood components administered and whether a TR occurred in women who received blood transfusions postpartum. Background controls were nonpregnant women who received blood transfusions during the study period. The study cohort consisted of 517 854 women. Of these, 12 183 (2.4%) received a blood transfusion. We identified 96 events involving a TR postpartum, giving a prevalence of 79 per 10 000 compared with 40 per 10 000 among nonpregnant women (odds ratio, 2.0; 95% confidence interval, 1.6-2.5). Preeclampsia was the single most important risk factor for TRs (odds ratio, 2.1; 95% confidence interval, 1.7-2.6). We conclude that special care should be taken when women with preeclampsia are considered for blood transfusion postpartum, because our findings indicate that pregnancy is associated with an increased risk for TRs.
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- 2019
25. Occupational exposure to organic particles and combustion products during pregnancy and birth outcome in a nationwide cohort study in Sweden
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Maria Albin, Lars Rylander, Filip Norlén, Magnus Westgren, Jenny Selander, Nils Plato, Per Gustavsson, and Pernilla Wiebert
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Adult ,medicine.medical_specialty ,organic dusts ,Job-exposure matrix ,Air Pollutants, Occupational ,010501 environmental sciences ,01 natural sciences ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Occupational Exposure ,Epidemiology ,medicine ,Humans ,Cooking ,030212 general & internal medicine ,Polycyclic Aromatic Hydrocarbons ,Workplace ,0105 earth and related environmental sciences ,Sweden ,Obstetrics ,business.industry ,Infant, Newborn ,Public Health, Environmental and Occupational Health ,Infant, Low Birth Weight ,medicine.disease ,Low birth weight ,Maternal Exposure ,Combustion products ,Infant, Small for Gestational Age ,Cohort ,Premature Birth ,Small for gestational age ,Female ,Particulate Matter ,epidemiology ,medicine.symptom ,female reproductive effects and adverse pregnancy outcomes ,business ,Oils ,Cohort study - Abstract
ObjectiveTo study if children of women exposed to organic particles and combustion products at work during pregnancy, have an increased risk of low birth weight, preterm birth or small for gestational age.MethodsA nationwide cohort of all occupationally active mothers and their children from single births during 1994 to the end of 2012 (1 182 138 observations) was formed. Information on birth outcome was obtained from the medical birth register. Information on absence from work, education, occupation, age, nationality and smoking habits was obtained from national registers. A job exposure matrix (FINJEM) was used to assess the exposure.ResultsPregnant women with low absence from work and high (>50th percentile) exposure to organic particles had an increased risk of giving birth to children with low birth weight (OR=1.19; 95% CI: 1.07 to 1.32), small for gestational age (OR=1.22; 95% CI: 1.07 to 1.38) or preterm birth (OR=1.17; 95% CI: 1.08 to 1.27). Subgroup analyses showed an increased risk of small for gestational age in association with exposure to oil mist. Exposure to oil mist and cooking fumes was associated with low birth weight. Paper and other organic dust was associated with preterm birth. Exposure to combustion products showed an increased risk of small for gestational age (OR=1.40; 95% CI: 1.15 to 1.71).ConclusionsThe results indicate that occupational exposure to organic particles or combustion products during pregnancy is associated with restriction of fetal growth and preterm birth. More studies are needed to confirm a casual association.
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- 2019
26. Automated analysis of fetal cardiac function using color tissue Doppler imaging in second half of normal pregnancy
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Lotta Herling, K. Ferm-Widlund, Ganesh Acharya, Nina Elmstedt, Jonas Johnson, Magnus Westgren, Sven-Erik Sonesson, Fredrik Bergholm, and Peter Lindgren
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Adult ,Cardiac function curve ,medicine.medical_specialty ,Heart Ventricles ,Diastole ,Gestational Age ,Doppler imaging ,03 medical and health sciences ,Fetal Heart ,Fetus ,0302 clinical medicine ,Pregnancy ,Reference Values ,Internal medicine ,medicine ,Humans ,VDP::Medisinske Fag: 700 ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Ultrasonography, Doppler, Color ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Color tissue ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,Echocardiography, Doppler ,VDP::Medical disciplines: 700 ,Cross-Sectional Studies ,Reproductive Medicine ,Cardiology ,Gestation ,Female ,business ,Fetal echocardiography ,Algorithms ,Blood Flow Velocity - Abstract
This is the pre-peer reviewed version of the following article: Herling, L., Johnse, J., Ferm-Widlund, K., Bergholm, F., Elmstedt, N, Lindgren, P. ... Westgren, M. (2018). Automated analysis of fetal cardiac funcion using color tissue Doppler imaging in second half of normal pregnancy. Ultrasound in Obstetrics & Gynecology, 53(3), 348-357, which has been published in final form at https://doi.org/10.1002/uog.19037. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Objectives - Color tissue Doppler imaging (cTDI) is a promising tool for the assessment of fetal cardiac function. However, the analysis of myocardial velocity traces is cumbersome and time‐consuming, limiting its application in clinical practice. The aim of this study was to evaluate fetal cardiac function during the second half of pregnancy and to develop reference ranges using an automated method to analyze cTDI recordings from a cardiac four‐chamber view. Methods - This was a cross‐sectional study including 201 normal singleton pregnancies between 18 and 42 weeks of gestation. During fetal echocardiography, a four‐chamber view of the heart was visualized and cTDI was performed. Regions of interest were positioned at the level of the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls of the fetal heart, to obtain myocardial velocity traces that were analyzed offline using the automated algorithm. Peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm) and rapid ventricular filling, i.e. early diastole (Em), as well as the Em/Am ratio, mechanical cardiac time intervals and myocardial performance index (cMPI) were evaluated, and gestational age‐specific reference ranges were constructed. Results - At 18 weeks of gestation, the peak myocardial velocities, presented as fitted mean with 95% CI, were: LV Am, 3.39 (3.09–3.70) cm/s; LV Sm, 1.62 (1.46–1.79) cm/s; LV Em, 1.95 (1.75–2.15) cm/s; septal Am, 3.07 (2.80–3.36) cm/s; septal Sm, 1.93 (1.81–2.06) cm/s; septal Em, 2.57 (2.32–2.84) cm/s; RV Am, 4.89 (4.59–5.20) cm/s; RV Sm, 2.31 (2.16–2.46) cm/s; and RV Em, 2.94 (2.69–3.21) cm/s. At 42 weeks of gestation, the peak myocardial velocities had increased to: LV Am, 4.25 (3.87–4.65) cm/s; LV Sm, 3.53 (3.19–3.89) cm/s; LV Em, 4.55 (4.18–4.94) cm/s; septal Am, 4.49 (4.17–4.82) cm/s; septal Sm, 3.36 (3.17–3.55) cm/s; septal Em, 3.76 (3.51–4.03) cm/s; RV Am, 6.52 (6.09–6.96) cm/s; RV Sm, 4.95 (4.59–5.32) cm/s; and RV Em, 5.42 (4.99–5.88) cm/s. The mechanical cardiac time intervals generally remained more stable throughout the second half of pregnancy, although, with increased gestational age, there was an increase in duration of septal and RV atrial contraction, LV pre‐ejection and septal and RV ventricular ejection, while there was a decrease in duration of septal postejection. Regression equations used for the construction of gestational age‐specific reference ranges for peak myocardial velocities, Em/Am ratios, mechanical cardiac time intervals and cMPI are presented. Conclusion - Peak myocardial velocities increase with gestational age, while the mechanical time intervals remain more stable throughout the second half of pregnancy. Using an automated method to analyze cTDI‐derived myocardial velocity traces, it was possible to construct reference ranges, which could be used in distinguishing between normal and abnormal fetal cardiac function.
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- 2019
27. Automated quantitative evaluation of fetal atrioventricular annular plane systolic excursion
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K. Ferm-Widlund, Ganesh Acharya, A Zamprakou, Magnus Westgren, Lotta Herling, and Jonas Johnson
- Subjects
Cardiac function curve ,medicine.medical_specialty ,Systole ,Heart Ventricles ,Population ,Gestational Age ,Ventricular Septum ,Doppler imaging ,Ultrasonography, Prenatal ,Fetal Heart ,Obstetrics and gynaecology ,Pregnancy ,Reference Values ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Interventricular septum ,education ,education.field_of_study ,Fetal Growth Retardation ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,Gestational age ,Stroke Volume ,General Medicine ,Echocardiography, Doppler, Color ,medicine.anatomical_structure ,Fetal Weight ,Reproductive Medicine ,Pulsatile Flow ,Atrioventricular Node ,Cardiology ,Feasibility Studies ,Gestation ,Female ,Tricuspid Valve ,business ,Fetal echocardiography ,Blood Flow Velocity - Abstract
OBJECTIVES The primary aim of this study was to evaluate the feasibility of automated measurement of fetal atrioventricular (AV) plane displacement (AVPD) over several cardiac cycles using myocardial velocity traces obtained by color tissue Doppler imaging (cTDI). The secondary objectives were to establish reference ranges for AVPD during the second half of normal pregnancy, to assess fetal AVPD in prolonged pregnancy in relation to adverse perinatal outcome and to evaluate AVPD in fetuses with a suspicion of intrauterine growth restriction (IUGR). METHODS The population used to develop the reference ranges consisted of women with an uncomplicated singleton pregnancy at 18-42 weeks of gestation (n = 201). The prolonged-pregnancy group comprised women with an uncomplicated singleton pregnancy at ≥ 41 + 0 weeks of gestation (n = 107). The third study cohort comprised women with a singleton pregnancy and suspicion of IUGR, defined as an estimated fetal weight 97.5th centile (n = 35). Cineloops of the four-chamber view of the fetal heart were recorded using cTDI. Regions of interest were placed at the AV plane in the left and right ventricular walls and the interventricular septum, and myocardial velocity traces were integrated and analyzed using an automated algorithm developed in-house to obtain mitral (MAPSE), tricuspid (TAPSE) and septal (SAPSE) annular plane systolic excursion. Gestational-age specific reference ranges were constructed and normalized for cardiac size. The correlation between AVPD measurements obtained using cTDI and those obtained by anatomic M-mode were evaluated, and agreement between these two methods was assessed using Bland-Altman analysis. The mean Z-scores of fetal AVPD in the cohort of prolonged pregnancies were compared between cases with normal and those with adverse outcome using Mann-Whitney U-test. The mean Z-scores of fetal AVPD in IUGR fetuses were compared with those in the normal reference population using Mann-Whitney U-test. Inter- and intraobserver variability for acquisition of cTDI recordings and offline analysis was assessed by calculating coefficients of variation (CV) using the root mean square method. RESULTS Fetal MAPSE, SAPSE and TAPSE increased with gestational age but did not change significantly when normalized for cardiac size. The fitted mean was highest for TAPSE throughout the second half of gestation, followed by SAPSE and MAPSE. There was a significant correlation between MAPSE (r = 0.64; P
- Published
- 2021
28. Severe Maternal Morbidity and Mortality Associated With COVID-19: The Risk Should not be Downplayed
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Karin Pettersson, Ganesh Acharya, Henrik Hagberg, and Magnus Westgren
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Adult ,medicine.medical_specialty ,Critical Care ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Population ,MEDLINE ,Maternal morbidity ,Risk Assessment ,Severity of Illness Index ,Special Editorial ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Environmental health ,Obstetrics and Gynaecology ,Severity of illness ,Pandemic ,medicine ,Humans ,Vulnerable population ,030212 general & internal medicine ,Pregnancy Complications, Infectious ,education ,Pandemics ,Sweden ,education.field_of_study ,030219 obstetrics & reproductive medicine ,SARS-CoV-2 ,business.industry ,Public health ,COVID-19 ,Obstetrics and Gynecology ,Health related ,General Medicine ,medicine.disease ,Respiration, Artificial ,Maternal Mortality ,Population data ,Puerperal Infection ,Female ,Coronavirus Infections ,Risk assessment ,business - Abstract
Nordic countries have a long tradition of collecting health related population data meticulously and reporting them transparently. Such data provide firm grounds for making good decisions and as a result the public health institutions in Scandinavia enjoy the trust of society. The Covid‐19 pandemic has, however, resulted in a completely new situation as we are now exploring in uncharted waters. Based on reports from China,1,2,3 Italy,4 USA5 and perhaps with the good intention of reducing anxiety among this vulnerable population group, it has been widely publicized that pregnant women are not at increased risk of susceptibility, infectivity and severity of COVID‐19 compared to the general population or non‐pregnant women, although a systematic review of 108 cases of laboratory confirmed pregnancies with COVID‐19 has reported the possibility of increased risk of severe disease among pregnant women.6
- Published
- 2021
29. Fetal and Maternal Safety Considerations for In Utero Therapy Clinical Trials: iFeTiS Consensus Statement
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Steven W. Shaw, Simon N. Waddington, Magnus Westgren, Citra Nurfarah Zaini Mattar, Cecilia Götherström, Jerry Kok Yen Chan, Anna L. David, Holm Schneider, Mahesh Choolani, Tippi C. MacKenzie, William H. Peranteau, Rachel Sagar, Christopher D. Porada, Agnes Jaulent, Graça Almeida-Porada, and Karin Blakemore
- Subjects
Pediatrics ,medicine.medical_specialty ,Statement (logic) ,Cell- and Tissue-Based Therapy ,Research & Experimental Medicine ,Pregnancy ,Drug Discovery ,Genetics ,Medicine ,Humans ,Adverse effect ,Molecular Biology ,Fetal therapy ,Pharmacology ,Genetics & Heredity ,Fetus ,Clinical Trials as Topic ,Fetal Therapies ,Science & Technology ,business.industry ,TRANSPLANTATION ,WOMEN ,Prenatal Care ,Genetic Therapy ,Clinical trial ,Biotechnology & Applied Microbiology ,Medicine, Research & Experimental ,ACCEPTABILITY ,In utero ,Perspective ,Molecular Medicine ,Female ,business ,Life Sciences & Biomedicine - Abstract
ispartof: MOLECULAR THERAPY vol:28 issue:11 pages:2316-2319 ispartof: location:United States status: published
- Published
- 2020
30. List of Contributors
- Author
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Ganesh Acharya, Michael Aertsen, Yalda Afshar, Cande V. Ananth, Michael Ashworth, Patrick Au, Spyros Bakalis, Guillaume Benoist, Colleen G. Bilancia, Caterina M. Bilardo, Louise D. Bryant, Colin R. Butler, Frank Van Calenbergh, Steve N. Caritis, Lyn S. Chitty, Patricia Collins, James Cook, Howard Cuckle, Anna L. David, Luc De Catte, Paolo De Coppi, Elisabeth de Jong-Pleij, Bart De Keersmaecker, Jan Deprest, Roland Devlieger, Guido M. de Wert, Jan E. Dickinson, Mark Dilworth, Wybo J. Dondorp, Caroline E. Dunk, Thomas R. Everett, Jane Fisher, Henry L. Galan, Mythily Ganapathi, Helena M. Gardiner, Cecilia Gotherstrom, Richard Harding, Jenny Hewison, Richard J. Hewitt, Liran Hiersch, Melissa Hill, Sara L. Hillman, An Hindryckx, Stuart B. Hooper, Berthold Huppertz, J. Ciaran Hutchinson, Jon Hyett, Luc Joyeux, Davor Jurkovic, John C. Kingdom, Sylvie Langlois, Lara S. Lemon, Marianne Leruez-Ville, Liesbeth Lewi, Brynn Levy, Y.W. Loke, Enrico Lopriore, George A. Macones, Fergal D. Malone, Anahit Martirosian, Fionnuala McAuliffe, Annie R.A. McDougall, Kenneth J. Moise, Ashley Moffett, Sieglinde M. Müllers, Ran Neiger, John P. Newnham, Sarah G. Obican, Anthony O. Odibo, Dick Oepkes, Pranav P. Pandya, Lawrence D. Platt, Rosalind Pratt, Kuhan Rajah, Rashmi Rao, Jute Richter, Joshua I. Rosenbloom, Francesca Maria Russo, Anthony R. Scialli, Neil J. Sebire, Andrew Sharkey, Susan C. Shelmerdine, Colin Sibley, Saul Snowise, Sylke Steggerda, Emily J. Su, Mary Tang, Arjan B. Te Pas, Alan T. Tita, Fred Ushakov, Ignatia B. Van den Veyver, Jeanine M. van Klink, Raman Venkataramanan, Yves Ville, Magdalena Walkiewicz, Colin Wallis, Lilian Walther-Jallow, Ronald J. Wapner, Magnus Westgren, Scott W. White, Louise C. Wilson, R. Douglas Wilson, Dian Winkelhorst, Paul J.D. Winyard, Christoph Wohlmuth, Karen Wou, Yuval Yaron, Kwok Yin Leung, and Angela Yulia
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- 2020
31. In Utero Stem Cell Transplantation
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Cecilia Götherström, Lilian Walther-Jallow, and Magnus Westgren
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- 2020
32. Automated analysis of fetal cardiac function using color tissue Doppler imaging
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Ganesh Acharya, Fredrik Bergholm, Peter Lindgren, Magnus Westgren, Jonas Johnson, Sven-Erik Sonesson, K. Ferm-Widlund, and Lotta Herling
- Subjects
Adult ,Male ,Cardiac function curve ,medicine.medical_specialty ,Fetal heart ,030204 cardiovascular system & hematology ,Doppler imaging ,Ultrasonography, Prenatal ,Pattern Recognition, Automated ,03 medical and health sciences ,Fetal Heart ,0302 clinical medicine ,Predictive Value of Tests ,Pregnancy ,Image Interpretation, Computer-Assisted ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Fetus ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Pregnancy Outcome ,Color tissue ,Obstetrics and Gynecology ,General Medicine ,Echocardiography, Doppler, Color ,Surgery ,Clinical Practice ,Cross-Sectional Studies ,Reproductive Medicine ,Female ,business ,Fetal echocardiography ,Blood Flow Velocity ,Biomedical engineering ,Automated method - Abstract
Objectives Our main objective was to evaluate the feasibility of an automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). Methods This was a prospective cross-sectional observational study of 107 singleton pregnancies in ≥41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest (ROI) were placed in the septum, right (RV) and left ventricular (LV) walls at the level of the atrioventricular plane (AV-plane). Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. Results A total of 321 myocardial velocity traces were analyzed by both methods. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured by the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and occasionally had considerable bias and precision for different cTDI parameters. Conclusions Automated analysis of myocardial velocity recordings obtained by cTDI was feasible suggesting that it could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function in both research and clinical practice.
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- 2018
33. Association of traction force and adverse neonatal outcome in vacuum-assisted vaginal delivery: A prospective cohort study
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Mats Blennow, Magnus Westgren, K Pettersson, and Gunilla Ajne
- Subjects
Adult ,medicine.medical_specialty ,Neonatal intensive care unit ,Vacuum Extraction, Obstetrical ,medicine.medical_treatment ,Clinical Decision-Making ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,Traction ,Intensive care ,Intensive Care Units, Neonatal ,Birth Injuries ,medicine ,Humans ,Fetal head ,030212 general & internal medicine ,Prospective cohort study ,Sweden ,030219 obstetrics & reproductive medicine ,Vaginal delivery ,Obstetrics ,business.industry ,Cesarean Section ,Infant, Newborn ,Obstetrics and Gynecology ,General Medicine ,Odds ratio ,Perioperative ,Traction (orthopedics) ,Obstetric Labor Complications ,Female ,Risk Adjustment ,business - Abstract
INTRODUCTION Traction force is a possible risk factor for adverse neonatal outcome in vacuum extraction delivery, but the knowledge is scarce and further investigation is needed. Our hypothesis was that high-level traction force increases the risk of admission to the neonatal intensive care unit. MATERIAL AND METHODS The study was a hospital-based prospective cohort study on low- and mid-vacuum extractions at the labor and delivery ward, Karolinska University Hospital, Huddinge, Sweden. Traction forces were measured in 331 women. An electronical handle was used to measure and register traction force. The main exposure variable was high-level traction force (≥75th percentile) during the first three pulls and the primary outcome was admission to the neonatal intensive care unit. Logistic regression was used to estimate the adjusted risk. RESULTS Among the exposed, 14/84 (16.7%) were admitted to neonatal intensive care, and among the unexposed 10/247 (4%). The crude odds ratio (OR) of admission to the neonatal intensive care unit when exposed to high-level traction force was 4.7, and the adjusted (birthweight, gestational length, cup detachment, number of pulls, duration, duration >15 minutes, mid-cavity fetal head station, failed extraction, indication and parity) OR was 2.85 (95% confidence interval [CI] 1.09-7.48). No significant effect was seen in Apgar scores
- Published
- 2019
34. Cellular Subsets of Maternal Microchimerism in Umbilical Cord Blood
- Author
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Anna Maria Jonsson Kanold, Magnus Westgren, and Cecilia Götherström
- Subjects
Adult ,0301 basic medicine ,T-Lymphocytes ,Biomedical Engineering ,CD34 ,umbilical cord blood collection ,lcsh:Medicine ,Cell Count ,Chimerism ,Polymorphism, Single Nucleotide ,Umbilical cord ,CD19 ,Maternal microchimerism ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Pregnancy ,medicine ,Humans ,Myeloid Cells ,Whole blood ,B-Lymphocytes ,Transplantation ,biology ,Cesarean Section ,Umbilical Cord Blood Transplantation ,business.industry ,Special Section: Cord Blood ,umbilical cord blood transplantation ,lcsh:R ,Cell Biology ,Delivery, Obstetric ,Fetal Blood ,Hematopoietic Stem Cells ,medicine.disease ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,Female ,cell trafficking ,Stem cell ,business ,030217 neurology & neurosurgery - Abstract
Maternal microchimerism may arise in the offspring during pregnancy, and may be favorable or unfavorable. Additionally, maternal cells present in umbilical cord blood used for stem cell transplantation may affect the outcome after transplantation. The aim of this study was to evaluate the cellular subset and frequency of maternal cells in umbilical cord blood following vaginal deliveries and elective Cesarean sections where the umbilical cord clamping time was measured. A total of 44 healthy women with normal pregnancies were included in the study. Of these, 24 delivered vaginally and 20 by elective Cesarean sections. In the fresh umbilical cord blood, cellular subsets of CD3+ (T-cells), CD19+ (B-cells), CD33+ (myeloid cells), CD34+ (hematopoietic progenitor cells) and CD56+ (natural killer cells) cells were isolated and DNA extracted. A single-nucleotide polymorphism unique to the mother was identified and maternal microchimerism in the different cellular fractions was detected using quantitative real-time polymerase chain reaction with a sensitivity of 0.01%. Overall, 5 out of the 44 (11%) umbilical cord blood samples contained maternal microchimerism. The positive fractions were total DNA (whole blood, n = 3), CD34+ ( n = 1), CD56+ ( n = 1) and CD34+/CD56+ ( n = 1). Overall, four of the five (80%) positive samples were from Cesarean sections and one was from a vaginal delivery. The conclusion from this study is that maternal microchimerism in umbilical cord blood is not a common phenomenon but includes both lymphoid and hematopoietic progenitor lineages.
- Published
- 2018
35. Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease
- Author
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Guido Moll, Lena Klingspor, Behnam Sadeghi, Olle Ringdén, Jacek Winiarski, Arjang Baygan, Britt Gustafsson, Mats Remberger, Magnus Westgren, and Bita Khoein
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Stromal cell ,Adolescent ,Placenta ,medicine.medical_treatment ,Mesenchymal stromal cells ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Human Clinical Articles ,Mesenchymal Stem Cell Transplantation ,Gastroenterology ,Young Adult ,03 medical and health sciences ,Human Clinical Article ,Acute graft‐versus‐host disease ,Pregnancy ,Internal medicine ,Decidua ,medicine ,Humans ,Transplantation, Homologous ,Child ,Aged ,Retrospective Studies ,Fetus ,business.industry ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,Infant ,Mesenchymal Stem Cells ,Cell Biology ,General Medicine ,Middle Aged ,Decidua stromal cells ,030104 developmental biology ,medicine.anatomical_structure ,Child, Preschool ,Allogeneic hematopoietic stem cell transplantation ,Female ,Bone marrow ,Stromal Cells ,Stem cell ,Complication ,business ,Developmental Biology - Abstract
Severe acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The placenta protects the fetus from the mother's immune system. We evaluated placenta-derived decidua stromal cells (DSCs), which differ from bone marrow mesenchymal stromal cells (BM-MSCs), as a treatment for severe acute GVHD. DSCs were obtained from term placentas. The DSCs were given to 38 patients with severe acute GVHD; 25 were steroid refractory (SR). DSCs were thawed and infused in buffer supplemented with either 10% AB plasma (group 1, n = 17), or 5% albumin (group 2, n = 21). The viability of cells was higher when thawed in albumin rather than AB plasma (p
- Published
- 2018
36. Fetal Mesenchymal Stromal Cells: an Opportunity for Prenatal Cellular Therapy
- Author
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Lilian Walther-Jallow, Magnus Westgren, Cecilia Götherström, Rachel Sagar, and Anna L. David
- Subjects
0301 basic medicine ,Fetus ,Genetic enhancement ,Mesenchymal stem cell ,Mesenchymal stromal cells ,Cell Biology ,In utero stem cell transplantation ,Biology ,Umbilical cord ,Transplantation ,Cell therapy ,03 medical and health sciences ,Paracrine signalling ,030104 developmental biology ,medicine.anatomical_structure ,Genetics ,Cancer research ,medicine ,Prenatal Therapies (WH Peranteau, Section Editor) ,Stem cell ,Prenatal therapy ,Molecular Biology ,Developmental Biology - Abstract
Purpose of Review The aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs). Recent Findings MSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and differentiate, or act via a paracrine effect on target tissues makes MSCs candidates for clinical therapies. Fetal and extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from adult sources. Summary MSCs may be safely transplanted prenatally via ultrasound-guided injection into the umbilical cord. Due to these characteristics, fetal MSCs are of great interest in the field of in utero stem cell transplantation for treatment of congenital disease.
- Published
- 2018
37. Fetal subcutaneous cells have potential for autologous tissue engineering
- Author
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Cecilia Götherström, Åsa Ekblad, Magdalena Fossum, and Magnus Westgren
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Population ,Biomedical Engineering ,Neovascularization, Physiologic ,Medicine (miscellaneous) ,Transplantation, Autologous ,Colony-Forming Units Assay ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,Fetus ,Subcutaneous Tissue ,0302 clinical medicine ,Tissue engineering ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,education ,Cellular Senescence ,Cell Proliferation ,education.field_of_study ,Tissue Engineering ,business.industry ,Mesenchymal stem cell ,Soft tissue ,Cell Differentiation ,Rats ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Collagen ,business ,Subcutaneous tissue - Abstract
Major congenital malformations affect up to 3% of newborns. Infants with prenatally diagnosed soft tissue defects should benefit from having autologous tissue readily available for surgical implantation in the perinatal period. In this study, we investigate fetal subcutaneous cells as cellular source for tissue engineering. Fetal subcutaneous biopsies were collected from elective terminations at gestational Week 20-21. Cells were isolated, expanded, and characterized in vitro. To determine cell coverage, localization, viability, and proliferation in different constructs, the cells were seeded onto a matrix (small intestine submucosa) or in collagen gel with or without poly(ε-caprolactone) mesh and were kept in culture for up to 8 weeks before analysis. Angiogenesis was analysed through a tube-forming assay. Fetal subcutaneous cells could be expanded until 43 ± 3 population doublings, expressed mesenchymal markers, and readily differentiate into adipogenic and osteogenic lineages. The cells showed low adherence to small intestine submucosa and did not migrate deep into the matrix. However, in collagen gels, the cells migrated into the gel and proliferated with sustained viability for up to 8 weeks. The cells in the matrices expressed Ki67, CD73, and α-smooth muscle actin but not cytokeratin or CD31. Fetal cells derived from subcutaneous tissue demonstrated favourable characteristics for preparation of autologous tissue transplants before birth. Our study supports the theory that cells could be obtained from the fetus during pregnancy for tissue engineering purposes after birth. In a future clinical situation, autologous transplants could be used for reconstructive surgery in severe congenital malformations.
- Published
- 2018
38. Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study
- Author
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Agneta Wikman, Magnus Westgren, Erle Refsum, Stellan Håkansson, and Anette Mörtberg
- Subjects
Register based ,Fetus ,Pediatrics ,medicine.medical_specialty ,Pregnancy ,030219 obstetrics & reproductive medicine ,business.industry ,Incidence (epidemiology) ,Immunology ,Gestational age ,Retrospective cohort study ,Hematology ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Neonatal alloimmune thrombocytopenia ,medicine ,Immunology and Allergy ,Gestation ,business - Abstract
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition, with an estimated incidence of one in 1000 to 2000 live births. Predominantly, FNAIT is due to maternal alloa ...
- Published
- 2017
39. Intensive care unit admissions for pregnant and nonpregnant women with coronavirus disease 2019
- Author
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Magnus Westgren and Ganesh Acharya
- Subjects
Pregnancy ,2019-20 coronavirus outbreak ,biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,biology.organism_classification ,medicine.disease_cause ,Intensive care unit ,Virology ,law.invention ,law ,Pandemic ,Medicine ,business ,Coronavirus Infections ,Betacoronavirus ,Coronavirus - Published
- 2020
40. Antenatal corticosteroid treatment and placental pathology, with a focus on villous maturation
- Author
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Miranda Um-Bergström, Marie-Therese Vinnars, Magnus Westgren, and Nikos Papadogiannakis
- Subjects
Adult ,medicine.medical_specialty ,Placenta Diseases ,Placenta ,Statistics as Topic ,Gestational Age ,Risk Assessment ,Preeclampsia ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,Glucocorticoids ,Retrospective Studies ,Sweden ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Confounding ,Infant, Newborn ,Obstetrics and Gynecology ,Gestational age ,Prenatal Care ,Retrospective cohort study ,General Medicine ,Odds ratio ,medicine.disease ,medicine.anatomical_structure ,Premature Birth ,Gestation ,Female ,Chorionic Villi ,business ,030217 neurology & neurosurgery - Abstract
Introduction Mothers at risk of preterm birth are treated with antenatal corticosteroids, which have advantageous effects for prematurely born infants. Accelerated villous maturation in the placenta is also associated with improved perinatal outcome. The primary aim of this study was to examine the association between antenatal corticosteroids and accelerated villous maturation. The secondary aim was to study associations with other placental pathologies. Material and methods A retrospective cohort study including 105 women who had (n = 75) or had not (n = 30) been treated with antenatal corticosteroids. The women gave birth between 22+0 and 26+6 weeks of gestation in Stockholm County between 1 April 2004 and 31 March 2007. A pathologist blinded to all clinical data except gestational age examined the placental slides to identify pathology parameters. The outcomes were correlated with antenatal corticosteroid treatment, and confounding factors were adjusted using logistic regression. Results Accelerated villous maturation was significantly higher in the group treated with corticosteroids (odds ratio 16, 95% CI 2.4–690, p = 0.0005). After adjustment for gestational age and preeclampsia, the difference remained significant (odds ratio 8.9, 95% CI 1.2–389, p = 0.021). No significant associations were found regarding the secondary outcome variables, after adjusting for possible confounders. Conclusions Antenatal corticosteroid treatment before preterm birth is associated with accelerated villous maturation. This could be one of the pathways by which corticosteroids are beneficial for preterm infants.
- Published
- 2017
41. Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?
- Author
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Lesley M. E. McCowan, May Ching Soh, Dharmintra Pasupathy, Magnus Westgren, and Catherine Nelson-Piercy
- Subjects
Adult ,Male ,medicine.medical_specialty ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Rheumatology ,Pregnancy ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pregnancy outcomes ,Intensive care medicine ,Metabolic Syndrome ,030203 arthritis & rheumatology ,Vascular disease ,business.industry ,Smoking ,Hypoxia (medical) ,Antiphospholipid Syndrome ,medicine.disease ,Pathophysiology ,Pregnancy Complications ,Cardiovascular Diseases ,Cohort ,Immunology ,Etiology ,Female ,medicine.symptom ,business ,Hydroxychloroquine - Abstract
Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal–placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.
- Published
- 2017
42. Massive Blood Transfusion in Relation to Delivery: Incidence, Trends, and Risk Factors: A Population-based Cohort Study
- Author
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Lars Thurn, Magnus Westgren, Agneta Wikman, and Pelle G. Lindqvist
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Placenta Accreta ,Hysterectomy ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Risk Factors ,medicine ,Humans ,Blood Transfusion ,Caesarean section ,education ,Abruptio Placentae ,Sweden ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Placental abruption ,Cesarean Section ,business.industry ,Obstetrics ,Incidence ,Incidence (epidemiology) ,Postpartum Hemorrhage ,Obstetrics and Gynecology ,Odds ratio ,Delivery, Obstetric ,medicine.disease ,Health Surveys ,Placenta previa ,Uterine rupture ,Massive blood transfusion ,Cohort ,Female ,Uterine Inertia ,business - Abstract
OBJECTIVE To estimate incidence, trends over time, and risk factors for massive blood transfusions in obstetric patients. A secondary aim was to evaluate transfusion ratios in relation to massive transfusion. DESIGN Population-based cohort. SETTING Five hospitals, in the Stockholm County, Sweden, from 1990 to 2011. POPULATION All women that gave birth in Stockholm county, Sweden, and who received blood transfusions postpartum between 1990 and 2011. METHODS Data on pregnancies and deliveries from the Swedish National Medical Birth Registry was cross-linked to the Stockholm transfusion database. Massive blood transfusion was defined as the transfusion of ≥10 units of red blood cells from partus through the next day. MAIN OUTCOME MEASURES Main primary outcome was massive blood transfusion postpartum. RESULTS Our cohort comprised 517 874 deliveries. Massive blood transfusion occurred in 277 women, for an incidence of 5.3 per 10 000 deliveries, and increased by 30% (P
- Published
- 2020
43. Characterisation of maternal human leukocyte antigen class I antibodies in suspected foetal and neonatal alloimmune thrombocytopenia
- Author
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Erle Refsum, Marie Reilly, Agneta Wikman, Stephan Meinke, Petter Höglund, Magnus Westgren, Jesper Dahl, Anette Mörtberg, and M.-K. Auvinen
- Subjects
biology ,business.industry ,Hematology ,Human leukocyte antigen ,030204 cardiovascular system & hematology ,medicine.disease ,Neonatal Thrombocytopenia ,03 medical and health sciences ,Human leukocyte antigen class I ,0302 clinical medicine ,Antigen ,Immunology ,Neonatal alloimmune thrombocytopenia ,medicine ,biology.protein ,Platelet ,Allele ,Antibody ,business ,030215 immunology - Abstract
SummaryObjectives To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). Background FNAIT occurs in 1 : 1–2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. Material and methods A total of 260 patient samples were referred between 2007 and 2012. Referrals with maternal HLA class I antibodies and no other cause for the neonatal thrombocytopenia were included for analysis (cases, n = 23). HPA-1a negative mothers were excluded. Control groups were screened positive mothers of healthy neonates (controls, n = 33) and female blood donors (blood donors, n = 19). LABScreen single antigen HLA class I beads was used for antibody analysis. Clinical records were reviewed for cases. Results All groups had broad antibody reactivity. Cases had more antibodies with high SFI levels compared with the controls (SFI>9999; medians 26, 6 and 0; P
- Published
- 2016
44. In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
- Author
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Claes-Göran Östenson, Albin Björk, Janne Lehtiö, Jorrit Boekel, Davide Tamburro, Yafeng Zhu, Maria Pernemalm, Magnus Westgren, Jochen M. Schwenk, Hanna Åmark, AnnSofi Sandberg, and Marie Wahren-Herlenius
- Subjects
Male ,Proteome ,QH301-705.5 ,Science ,Biology ,Bioinformatics ,Proteomics ,General Biochemistry, Genetics and Molecular Biology ,proteomics ,Pregnancy ,Tandem Mass Spectrometry ,Placenta ,biomarker discovery ,medicine ,Humans ,Biology (General) ,Human Biology and Medicine ,Maternal-Fetal Exchange ,plasma ,mass spectrometry ,General Immunology and Microbiology ,General Neuroscience ,Protein transfer ,Child birth ,Blood Proteins ,General Medicine ,medicine.disease ,Blood proteins ,Healthy Volunteers ,Tools and Resources ,Protein Transport ,medicine.anatomical_structure ,Human plasma ,proteogenomics ,Medicine ,Female ,Isoelectric Focusing ,Computational and Systems Biology ,Human ,Chromatography, Liquid - Abstract
Here, we present a method for in-depth human plasma proteome analysis based on high-resolution isoelectric focusing HiRIEF LC-MS/MS, demonstrating high proteome coverage, reproducibility and the potential for liquid biopsy protein profiling. By integrating genomic sequence information to the MS-based plasma proteome analysis, we enable detection of single amino acid variants and for the first time demonstrate transfer of multiple protein variants between mother and fetus across the placenta. We further show that our method has the ability to detect both low abundance tissue-annotated proteins and phosphorylated proteins in plasma, as well as quantitate differences in plasma proteomes between the mother and the newborn as well as changes related to pregnancy., eLife digest Blood cells travel through the blood vessels in a soupy mixture of proteins called plasma. Most of these proteins are plasma-specific, yet small amounts of proteins can leak into the plasma from other body parts and may provide hints about what is going on elsewhere in the body. This could allow doctors to use plasma samples to assess health or detect disease. But so far developing methods to detect these leaked proteins has proved difficult. Plasma passing through the placenta can transfer proteins between a pregnant woman and her baby. Learning more about these protein exchanges may help scientists understand how the mother and baby adapt to each other and what triggers child birth. But, so far, they have been hard to study. Using DNA to help trace the origins of proteins found in mother or baby could make it easier. Now, Pernemalm et al. have used DNA sequencing in combination with protein analysis to identify proteins passed between two pregnant mothers and their babies. Comparing the genetic sequences of each mother and child made it possible to trace the origin of the proteins. For example, if a mother had a version of the protein that matched genes the child inherited from its father, they knew it passed from the baby to the mother. This approach found 24 proteins in plasma from two pregnant mothers that had likely passed through the placenta during pregnancy. Pernemalm et al. also analyzed the plasma of 30 healthy individuals and confirmed that it contained several proteins that had likely leaked from other organs, including the lungs and pancreas. Monitoring protein transfer between pregnant mother and baby may help scientists identify what triggers normal or premature deliveries. One advantage of the technique developed Pernemalm et al. is that it can analyze plasma proteins from large numbers of people, which could enable larger studies. More refinement of the technique may also allow scientists to identify leaked proteins in the plasma that provide an early warning of cancer or other diseases.
- Published
- 2019
45. Author response: In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta
- Author
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Janne Lehtiö, Claes-Göran Östenson, Albin Björk, Jochen M. Schwenk, Davide Tamburro, Yafeng Zhu, Jorrit Boekel, Hanna Åmark, Magnus Westgren, Maria Pernemalm, AnnSofi Sandberg, and Marie Wahren-Herlenius
- Subjects
medicine.anatomical_structure ,Human plasma ,Chemistry ,Placenta ,Proteome ,medicine ,Cell biology - Published
- 2019
46. Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease
- Author
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Britt Gustafsson, Olle Ringdén, Jacek Winiarski, M Remberger, Behnam Sadeghi, Magnus Westgren, Bita Khoein, Jonas Mattsson, Gianluca Moretti, and Lena Klingspor
- Subjects
Adult ,Male ,medicine.medical_specialty ,Stromal cell ,Adolescent ,Survival ,Placenta ,Graft vs Host Disease ,Pilot Projects ,Gastroenterology ,Graft-versus-host disease ,Young Adult ,03 medical and health sciences ,Steroid-resistant GVHD ,0302 clinical medicine ,Pregnancy ,Internal medicine ,Decidua ,medicine ,Humans ,Cumulative incidence ,Prospective Studies ,Hematologi ,Child ,Long-term follow-up ,Aged ,Transplantation ,Fetus ,Hematology ,business.industry ,Infant ,Middle Aged ,medicine.disease ,Survival Analysis ,Decidua stromal cells ,Bronchiolitis ,Child, Preschool ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Stromal Cells ,business ,Follow-Up Studies ,030215 immunology - Abstract
There is a need for effective therapy with few side effects for severe acute graft-versus-host disease (GVHD). The placenta protects the fetus from the mother's haploidentical immune system during pregnancy. We found that maternal stromal cells from the fetal membrane, so-called decidua stromal cells (DSCs), are more immunosuppressive than other sources of stromal cells. We prospectively treated 21 patients (median age, 49 years; range, 1.6 to 72 years) for grade II-IV acute GVHD. All 21 patients had biopsy-proven gastrointestinal GVHD. The majority of patients were either steroid-refractory or had progressive GVHD, 11 patients after >7 days or with progression after 3 days, and 10 were refractory to steroids after >3 days. We used an improved protocol in which DSCs were thawed and infused in a buffer with 5% human albumin. DSCs were given at a median dose of 1.2 (range, 0.9 to 2.9) × 106 cells/kg body weight with a median of 2 (range, 1 to 6) doses, given 1 week apart. The median viability of thawed DSCs was 93% (range, 69% to 100%), and the median cell passage number was 4 (range, 2 to 4). Complete resolution of GVHD was seen in 11 patients, with a partial response in the other 10. The cumulative incidence of chronic GVHD was 52%. GVHD was mild in 6 patients, moderate in 4 patients, and severe in 1 patient based on National Institutes of Health chronic GVHD severity scoring. Nine patients died, including 3 from relapse and 1 each from acute GVHD and septicemia, Zygomycetes infection, liver insufficiency, cerebral hemorrhage, multiple organ failure, and chronic GVHD with obstructive bronchiolitis. Four-year transplantation-related mortality was 28.6%, and overall survival was 57%. Survival was similar (P = .33) to that for all 293 patients who underwent allogeneic hematopoietic cell transplantation during the same period (2012 to 2015), with 66% overall survival. DSC infusion is a novel therapy for acute GVHD grade II-IV, and a randomized trial is currently underway (ClinicalTrials.gov NCT 02172937).
- Published
- 2019
47. Genetic Analysis of Copy Number Variation in Large Chorangiomas
- Author
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Magnus Westgren, Meeli Sirotkina, Konstantinos Douroudis, and Nikos Papadogiannakis
- Subjects
DNA Copy Number Variations ,Placenta ,Gestational Age ,Biology ,Genetic analysis ,Pathology and Forensic Medicine ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,Segmental Duplications, Genomic ,Pregnancy ,medicine ,Humans ,Copy-number variation ,Genetic Testing ,Sequence Deletion ,Genetics ,Comparative Genomic Hybridization ,030219 obstetrics & reproductive medicine ,Incidence (epidemiology) ,Chorangiomas ,Chorangioma ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Female ,medicine.symptom ,Hemangioma ,Comparative genomic hybridization - Abstract
Introduction Chorangioma (CA) is the most common nontrophoblastic, vascular tumor-like lesion of the placenta with a reported incidence of 0.5% to 1% in all examined placentas. The underlying molecular mechanisms of CAs are still poorly elucidated, and a systematic investigation of the genetic background of CAs has not previously been done. Materials and Methods Tissue biopsies from 8 large (>40 mm) histologically confirmed CAs and 8 unaffected matched placenta controls, along with standard control DNA samples were analyzed for large genomic deletions and duplications using array comparative genomic hybridization (array-CGH) method. Results Array-CGH analysis revealed no rare or novel copy number variants in the CA samples compared with either standard control DNA or unaffected placenta DNA from the same individual. Discussion In this study, a systematic genetic investigation of 8 large CAs failed to demonstrate any large-scale pathogenic genetic changes. This lack of association might support a nongenetic, nontumorous origin of these lesions; however, additional genetic studies focusing on smaller genomic alterations are required to fully assess any possible genetic contribution.
- Published
- 2018
48. Fetal CD103+ IL-17–Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid
- Author
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Magnus Westgren, Jenny Mjösberg, Jakob Michaëlsson, Liv Eidsmo, Elisabet Åkesson, Elisa Martini, Martin A. Ivarsson, Åke Seiger, Gunilla Tegerstedt, Erik Sundström, Nicole Marquardt, Sverker Ek, Danielle Friberg, and Marius Kublickas
- Subjects
0301 basic medicine ,Amniotic fluid ,Immunology ,Population ,Inflammation ,Respiratory Mucosa ,Biology ,03 medical and health sciences ,Fetus ,Immune system ,Antigens, CD ,Pregnancy ,Immunity ,medicine ,Humans ,Immunology and Allergy ,Lymphocytes ,Intestinal Mucosa ,education ,Cells, Cultured ,education.field_of_study ,Tumor Necrosis Factor-alpha ,Interleukin-17 ,Innate lymphoid cell ,Infant, Newborn ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,Amniotic Fluid ,Immunity, Innate ,Lymphocyte Subsets ,030104 developmental biology ,Pregnancy Trimester, Second ,Leukocyte Common Antigens ,Female ,Tumor necrosis factor alpha ,medicine.symptom ,Integrin alpha Chains - Abstract
Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45+ cells in AF is represented by a subset of fetal CD103+ group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF. Fetal CD103+ ILC3s could also be detected at high frequency in second-trimester mucosal tissues (e.g., the intestine and lung). Taken together, our data indicate that CD103+ ILC3s accumulate with gestation in the fetal intestine and subsequently egress to the AF. The dominance of ILC3s producing IL-17 and TNF in AF suggests that they could be involved in controlling intra-amniotic infections and inflammation and as such could be important players in regulating subsequent premature birth.
- Published
- 2016
49. Prenatal ultrasound and childhood autism: long-term follow-up after a randomized controlled trial of first-vssecond-trimester ultrasound
- Author
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Christopher Gillberg, S. Saltvedt, Joakim Westerlund, Elisabeth Fernell, L. Höglund Carlsson, Magnus Westgren, and Britt-Marie Anderlid
- Subjects
Pregnancy ,Pediatrics ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,business.industry ,Ultrasound ,Obstetrics and Gynecology ,Gestational age ,General Medicine ,medicine.disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Reproductive Medicine ,Randomized controlled trial ,Autism spectrum disorder ,law ,Cohort ,medicine ,Autism ,Gestation ,Radiology, Nuclear Medicine and imaging ,business ,030217 neurology & neurosurgery - Abstract
Objective To analyze whether the frequency of autism spectrum disorder (ASD) in a cohort of Swedish children differs between those exposed to ultrasound in the 12th week and those exposed to ultrasound in the 18th week of gestation. Methods The study cohort consisted of approximately 30 000 children born between 1999 and 2003 to mothers who had been randomized to a prenatal ultrasound examination at either 12 or 18 weeks' gestation as part of the framework for a study on nuchal translucency screening. The outcome measure in the present study was the rate of ASD diagnoses among the children. Information on ASD diagnoses was based on data from the Swedish social insurance agency concerning childcare allowance granted for ASD. Results Between 1999 and 2003, a total of 14 726 children were born to women who underwent a 12-week ultrasound examination and 14 596 to women who underwent an 18-week ultrasound examination. Of these, 181 (1.2%) and 176 (1.2%) children, respectively, had been diagnosed with ASD. There was no difference in ASD frequency between the early and late ultrasound groups. Conclusions Women subjected to at least one prenatal ultrasound examination at either 12 or 18 weeks' gestation had children with similar rates of ASD. However, this result reflects routine care 10–15 years ago in Sweden. Today, higher intensity ultrasound scans are performed more frequently, at earlier stages during pregnancy and for non-medical purposes, implying longer exposure time for the fetus. This change in the use of ultrasound necessitates further follow-up study of the possible effects that high exposure to ultrasound during the gestational period has on the developing brain. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
- Published
- 2016
50. Cost-effectiveness of first trimester non-invasive fetalRHDscreening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis
- Author
-
Agneta Wikman, Magnus Westgren, Marius Kublickas, Eleonor Tiblad, Martin Neovius, and Kristian Neovius
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Cost effectiveness ,Cost-Benefit Analysis ,Rho(D) Immune Globulin ,medicine.medical_treatment ,Population ,Rh Isoimmunization ,Sensitivity and Specificity ,Rho(D) immune globulin ,Targeted therapy ,Cohort Studies ,Erythroblastosis, Fetal ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,Immunologic Factors ,Mass Screening ,030212 general & internal medicine ,education ,health care economics and organizations ,Mass screening ,Sweden ,education.field_of_study ,Hematologic Tests ,030219 obstetrics & reproductive medicine ,Cost–benefit analysis ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Health Services ,medicine.disease ,Pregnancy Trimester, First ,Female ,business ,medicine.drug ,Cohort study - Abstract
Objective To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. Design Model based on a population-based cohort study. Setting The Swedish health service. Population Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010–2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008–2009 when standard care did not include RAADP (n = 7099). Methods Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. Main outcome measure Additional cost per RhD immunisation averted. Results Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. Conclusion Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. Tweetable abstract Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.
- Published
- 2015
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