Publications by authors named "Magnus Westgren"

123 Publications

Perinatal outcome after vacuum assisted delivery with digital feedback on traction force; a randomised controlled study.

BMC Pregnancy Childbirth 2021 Feb 26;21(1):165. Epub 2021 Feb 26.

Pregnancy Care & Delivery K57, Karolinska University Hospital, 141 86, Stockholm, Sweden.

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 < 0.05). A recalculation of power revealed that 800 cases would be needed in each group to show a decrease in primary outcome from three to 1 %. This was not feasible, and the study therefore closed.

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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http://dx.doi.org/10.1186/s12884-021-03604-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913459PMC
February 2021

Fetal and Maternal Safety Considerations for In Utero Therapy Clinical Trials: iFeTiS Consensus Statement.

Mol Ther 2020 11 16;28(11):2316-2319. Epub 2020 Oct 16.

Prenatal Cell and Gene Therapy Group, Elizabeth Garrett Anderson Institute for Women's Health, University College London, London WC1E 6HX, UK; NIHR University College London Hospitals Biomedical Research Centre, 149 Tottenham Court Road, London W1T 7DN, UK; Department of Development and Regeneration, Katholieke Universiteit, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.ymthe.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647692PMC
November 2020

Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings.

Cardiovasc Ultrasound 2020 Aug 13;18(1):34. Epub 2020 Aug 13.

Department of Clinical Science, Intervention and Technology - CLINTEC, Karolinska Institutet, Stockholm, Sweden.

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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http://dx.doi.org/10.1186/s12947-020-00214-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427079PMC
August 2020

Intensive care unit admissions for pregnant and nonpregnant women with coronavirus disease 2019.

Am J Obstet Gynecol 2020 11 25;223(5):779-780. Epub 2020 Jul 25.

Division of Obstetrics & Gynaecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm 141 86, Sweden.

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http://dx.doi.org/10.1016/j.ajog.2020.07.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382351PMC
November 2020

Association of traction force and adverse neonatal outcome in vacuum-assisted vaginal delivery: A prospective cohort study.

Acta Obstet Gynecol Scand 2020 12 9;99(12):1710-1716. Epub 2020 Sep 9.

Children and Women's Health, Karolinska University Hospital, Stockholm, Sweden.

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 <7 at 5 minutes or pH <7.1.

Conclusions: High-level traction force may be a risk factor for neonatal complications. Although these results do not mandate any alterations in clinical guidelines, perioperative feedback on traction force may be useful to alert the obstetrician to a timely conversion to cesarean section. To study plausible traction force specific outcomes such as head traumas, a larger sample size is required.
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http://dx.doi.org/10.1111/aogs.13952DOI Listing
December 2020

Is obesity in pregnancy associated with signs of chronic fetal hypoxia?

Acta Obstet Gynecol Scand 2020 12 3;99(12):1649-1656. Epub 2020 Jul 3.

Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Karolinska Institute, Södersjukhuset Hospital, Stockholm, Sweden.

Introduction: The prevalence of obesity in pregnancy is increasing worldwide. Maternal obesity increases risks of severe fetal and neonatal complications. The underlying pathophysiological mechanisms are unclear. One possible contributing factor could be chronic fetal hypoxia. The aim of this study was to compare placentas from women with and without obesity with respect to placental lesions, which could reflect compensatory mechanisms in response to chronic fetal hypoxia as well as lesions possibly leading to chronic fetal hypoxia. In addition, levels of erythropoietin in cord blood were compared between offspring of lean and obese women.

Material And Methods: This cohort study included 180 women with uneventful, full-term, singleton pregnancies, out of which 91 lean women had a body mass index (BMI) of 18.5-24.9 kg/m and 89 women had obesity (BMI ≥30 kg/m ). Women were recruited at Södersjukhuset between 16 October 2018 and 2 December 2019. Placentas were investigated by two senior perinatal pathologists, who were blinded for maternal BMI. Cord blood was analyzed for levels of erythropoietin.

Results: Levels of erythropoietin in cord blood increased with maternal BMI (P = .01, β = 0.97, 95% CI 0.27-1.68). There was no difference between placentas of obese and lean women in number of placental lesions reflecting chronic fetal hypoxia or in lesions that could possibly lead to chronic fetal hypoxia.

Conclusions: This study of term and uneventful pregnancies demonstrated a positive association between maternal obesity and concentrations of erythropoietin in cord blood at birth. This finding supports the hypothesis of chronic fetal hypoxia as a risk factor for complications in the pregnancies of obese women. There were no differences in lesions associated with hypoxia between placentas of obese and lean women.
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http://dx.doi.org/10.1111/aogs.13941DOI Listing
December 2020

Severe maternal morbidity and mortality associated with COVID-19: The risk should not be downplayed.

Acta Obstet Gynecol Scand 2020 07 13;99(7):815-816. Epub 2020 Jun 13.

Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1111/aogs.13900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273078PMC
July 2020

A new microdialysis probe for continuous lactate measurement during fetal monitoring: Proof of concept in an animal model.

Acta Obstet Gynecol Scand 2020 10 21;99(10):1411-1416. Epub 2020 Apr 21.

Department of Obstetrics & Gynecology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

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 , 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 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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http://dx.doi.org/10.1111/aogs.13865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540415PMC
October 2020

Prenatal stem cell therapy for inherited diseases: Past, present, and future treatment strategies.

Stem Cells Transl Med 2020 Feb 24;9(2):148-157. Epub 2019 Oct 24.

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.

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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http://dx.doi.org/10.1002/sctm.19-0107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988764PMC
February 2020

Incidence and risk factors of transfusion reactions in postpartum blood transfusions.

Blood Adv 2019 08;3(15):2298-2306

Department of Clinical Sciences and Education, Karolinska Institutet, Stockholm, Sweden; and.

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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http://dx.doi.org/10.1182/bloodadvances.2019000074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693016PMC
August 2019

Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2019 10 4;25(10):1965-1969. Epub 2019 Jun 4.

Translational Cell Therapy Research, Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institute, Huddinge, Sweden.

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) × 10 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 NCT02172937).
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http://dx.doi.org/10.1016/j.bbmt.2019.05.034DOI Listing
October 2019

Occupational exposure to organic particles and combustion products during pregnancy and birth outcome in a nationwide cohort study in Sweden.

Occup Environ Med 2019 08 23;76(8):537-544. Epub 2019 May 23.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Objective: To 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.

Methods: A 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.

Results: Pregnant 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).

Conclusions: The 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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http://dx.doi.org/10.1136/oemed-2018-105672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703147PMC
August 2019

In-depth human plasma proteome analysis captures tissue proteins and transfer of protein variants across the placenta.

Elife 2019 04 8;8. Epub 2019 Apr 8.

Karolinska Institute, Stockholm, Sweden.

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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http://dx.doi.org/10.7554/eLife.41608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519984PMC
April 2019

Effect of team training and monitoring on the rate of failed mid and low cavity vacuum extraction: a hospital based intervention study.

BMC Pregnancy Childbirth 2019 Mar 29;19(1):101. Epub 2019 Mar 29.

Department of Obstetrics and Gynecology, Karolinska University Hospital at Huddinge, K57, 141 86, Stockholm, Sweden.

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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http://dx.doi.org/10.1186/s12884-019-2257-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440163PMC
March 2019

Stakeholder views and attitudes towards prenatal and postnatal transplantation of fetal mesenchymal stem cells to treat Osteogenesis Imperfecta.

Eur J Hum Genet 2019 08 27;27(8):1244-1253. Epub 2019 Mar 27.

North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial is investigating the safety and efficacy of transplanting fetal derived mesenchymal stromal cells (MSCs) prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI). This study aimed to explore stakeholder views to understand perceived benefits or concerns, identify ethical issues and establish protocols for support and counselling. Semi-structured qualitative interviews were conducted with three groups; 1. Adults affected with OI, with and without children, and parents of children affected with OI; 2. Health professionals who work with patients with OI; 3. Patient advocates from relevant patient support groups. Interviews were digitally recorded, transcribed verbatim and analysed using thematic analysis. Interviews with 56 participants revealed generally positive views towards using fetal MSC transplantation to treat OI. Early treatment was considered advantageous for preventing fractures and reducing severity and could bring psychological benefits for parents. Common concerns were procedure safety, short/long-term side effects and whether transplantation would be effective. Difficulties inherent in decision-making were frequently discussed, as treatment efficacy is unknown and, by necessity, parents will make decisions at a time when they are vulnerable. Support needs may differ where there is a family history of OI compared to an unexpected diagnosis of OI. Explaining fetal MSC transplantation in a way that all parents can understand, clear expectation setting, psychological support and time for reflection during the decision-making process will be crucial to allow parents to make informed decisions about participation in the BOOSTB4 clinical trial.
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http://dx.doi.org/10.1038/s41431-019-0387-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777523PMC
August 2019

Fetal stem cell transplantation and gene therapy.

Best Pract Res Clin Obstet Gynaecol 2019 Jul 5;58:142-153. Epub 2019 Mar 5.

Department of Clinical Science, Intervention and Technology, K57, Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge Karolinska Institutet, Stockholm, Sweden. Electronic address:

The present chapter summarizes our current knowledge on fetal stem cell and gene therapy. It focuses on these therapeutic alternatives in regard to past experiences and ongoing and planned studies in humans. Several methodological challenges are discussed that may have wide implications on how these methods could be introduced in clinical practices. Although still promising, the methods are afflicted with very special requirements not least in regard to safety and ethical questions. Furthermore, careful monitoring and extended follow-up of the child and his/hers mother who receive prenatal stem cell or gene treatments are of outmost importance. Taken these prerequisites into consideration, it is natural that this type of experimental fetal therapies requires collaboration between different disciplinaries and institutions within medicine.
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http://dx.doi.org/10.1016/j.bpobgyn.2019.02.007DOI Listing
July 2019

Occupational exposure to inorganic particles during pregnancy and birth outcomes: a nationwide cohort study in Sweden.

BMJ Open 2019 02 27;9(2):e023879. Epub 2019 Feb 27.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Objectives: The aim of this study was to investigate if occupational exposure to inorganic particles or welding fumes during pregnancy is associated with negative birth outcomes.

Design: A prospective national cohort study.

Setting: All single births from 1994 to 2012 in Sweden. Information on birth weight, preterm birth, small for gestational age, smoking habits, nationality, age, occupation, absence from work and education was obtained from nationwide registers. Exposure to inorganic particles (mg/m) was assessed from a job exposure matrix.

Participants: This study included all single births by occupationally active mothers (995 843).

Outcome Measures: Associations between occupational exposures and negative birth outcomes in the form of low birth weight, preterm birth and small for gestational age.

Results: Mothers who had high exposure to inorganic particles and had less than 50 days (median) of absence from work during pregnancy showed an increased risk of preterm birth (OR 1.18; 95% CI 1.07 to 1.30), low birth weight (OR 1.32; 95% CI 1.18 to 1.48) as well as small for gestational age (OR 1.20; 95% CI 1.04 to 1.39). The increased risks were driven by exposure to iron particles. No increased risks were found in association with exposure to stone and concrete particles. High exposure to welding fumes was associated with an increased risk of low birth weight (OR 1.22; 95% CI 1.02 to 1.45) and preterm birth (OR 1.24; 95% CI 1.07 to 1.42).

Conclusions: The results indicate that pregnant women should not be exposed to high levels of iron particles or welding fumes.
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http://dx.doi.org/10.1136/bmjopen-2018-023879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398675PMC
February 2019

Prediction of large-for-gestational-age infants in pregnancies complicated by obesity: A population-based cohort study.

Acta Obstet Gynecol Scand 2019 06 24;98(6):769-776. Epub 2019 Feb 24.

Department of Clinical Science and Education, Unit of Obstetrics and Gynecology, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.

Introduction: Infants born large for gestational age (LGA) have increased risks of adverse perinatal outcomes. Maternal obesity, defined as body mass index (BMI) ≥30 kg/m , is one of the most prevalent risk factors for LGA and the proportion of pregnancies complicated by obesity is increasing. Early identification of women with BMI ≥30 kg/m at increased risk of giving birth to an LGA infant may open possibilities for prevention, aiming at decreasing the incidence of LGA.

Material And Methods: A population-based cohort study using information from the first-trimester screening database, which was cross-linked with the Swedish Medical Birth Register. The database included 139 277 full-term singletons without fetal anomalies born between 2006 and 2015 to mothers without prepregnancy diabetes. Of these, 9.1% (n = 12 704) were infants of mothers with BMI ≥30 kg/m . For all women with BMI ≥30 kg/m , a prediction model for LGA to be used in early pregnancy was constructed based on information on biochemical markers and maternal characteristics. A similar model, as well as a prepregnancy prediction model, were constructed for parous women with BMI ≥30 kg/m . In parous women, data from the previous pregnancy were also used. Receiver operating characteristic curve and area under curve (AUC) were calculated.

Results: The predictive models for LGA in parous women with BMI ≥30 kg/m prepregnancy and in early pregnancy had AUCs of 0.80 (95% CI 0.78-0.82) and 0.81 (95% CI 0.79-0.82), respectively. For all women with BMI ≥30 kg/m , the prediction of LGA in early pregnancy had an AUC of 0.66 (95% CI 0.64-0.67).

Conclusions: Performance of the prepregnancy and early pregnancy prediction models for LGA in parous women with BMI ≥30 kg/m was good. The predictive capacity was largely driven by previous child's birthweight. First-trimester measurements of fetal size did not improve the predictive capacity in parous women. Predictions of LGA in all women with BMI ≥30 kg/m in early pregnancy, without taking previous child's birthweight into account, remain difficult.
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http://dx.doi.org/10.1111/aogs.13546DOI Listing
June 2019

Genetic Analysis of Copy Number Variation in Large Chorangiomas.

Pediatr Dev Pathol 2019 May-Jun;22(3):236-242. Epub 2018 Nov 14.

1 Section of Perinatal Pathology, Department of Pathology, Karolinska University Hospital Huddinge, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1177/1093526618811744DOI Listing
September 2019

Cellular Subsets of Maternal Microchimerism in Umbilical Cord Blood.

Cell Transplant 2019 05 27;28(5):522-528. Epub 2018 Jun 27.

1 Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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, = 3), CD34+ ( = 1), CD56+ ( = 1) and CD34+/CD56+ ( = 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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http://dx.doi.org/10.1177/0963689718779783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103608PMC
May 2019

Fetal Mesenchymal Stromal Cells: an Opportunity for Prenatal Cellular Therapy.

Curr Stem Cell Rep 2018 15;4(1):61-68. Epub 2018 Feb 15.

2Department of Clinical Science, Intervention and Technology, K57, Division of Obstetrics and Gynecology, Karolinska University Hospital Huddinge, Karolinska Institutet, 141 86 Stockholm, Sweden.

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.
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http://dx.doi.org/10.1007/s40778-018-0118-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866262PMC
February 2018

Imaging single DNA molecules for high precision NIPT.

Sci Rep 2018 03 14;8(1):4549. Epub 2018 Mar 14.

Harris Birthright Research Centre for Fetal Medicine, London, UK.

Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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http://dx.doi.org/10.1038/s41598-018-22606-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852104PMC
March 2018

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease.

Stem Cells Transl Med 2018 04 13;7(4):325-331. Epub 2018 Mar 13.

Translational Cell Therapy Research (TCR), Department of Laboratory Medicine.

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 < .001). Group 1 received a higher cell dose (p < .001), cells of lower passage number (p < .001), and fewer infusions (p = .002) than group 2. The GVHD response (no/partial/complete) was 7/5/5 in group 1 and 0/10/11 in group 2 (p = .01). One-year survival in the two groups was 47% (95% confidence interval [CI] 23-68) and 76% (95% CI 51-89), respectively (p = .016). For the SR patients, 1-year survival was 73% (95% CI 37-90) in SR group 2 (n = 11), which was better than 31% (95% CI 11-54) in SR group 1 (n = 13; p = .02), 20% (95% CI 5-42) in BM-MSC treated (n = 15; p = .0015), and 3% (95% CI 0-14) in historic controls (n = 32; p < .001). DSCs are a promising new treatment for severe acute GVHD. Prospective randomized trials are needed for evaluation of efficacy. (Clinical trial NCT-02172937.) Stem Cells Translational Medicine 2018;7:325-332.
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http://dx.doi.org/10.1002/sctm.17-0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866941PMC
April 2018

Fetal subcutaneous cells have potential for autologous tissue engineering.

J Tissue Eng Regen Med 2018 05 12;12(5):1177-1185. Epub 2018 Feb 12.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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.
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http://dx.doi.org/10.1002/term.2639DOI Listing
May 2018

Wait a minute? An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping.

BMJ Open 2017 12 29;7(12):e017215. Epub 2017 Dec 29.

Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.

Background And Objective: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping.

Design: Prospective observational study with two historical controls.

Setting: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden.

Methods: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery.

Results: After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29).

Conclusion: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency.

Trial Registration Number: NCT01245296.
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http://dx.doi.org/10.1136/bmjopen-2017-017215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778270PMC
December 2017

Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study.

Transfusion 2018 01 8;58(1):223-231. Epub 2017 Nov 8.

Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden.

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 alloantibodies that target paternally derived human platelet antigen (HPA) 1a. The most feared complication is an intracranial hemorrhage (ICH). The aim of this study was to determine the frequency of associated maternal platelet (PLT) alloimmunization in a population of neonates born from 32 weeks of gestation and diagnosed with an ICH.

Study Design And Methods: The Swedish Neonatal Quality (SNQ) register was used to identify neonates diagnosed with an ICH born between 2003 and 2012. Mothers were invited to donate peripheral blood, to investigate their HPA-1a antigen status, and test for anti-HPA and anti-HLA Class I alloantibodies. Clinical data for the neonates were retrieved from the SNQ register and available clinical records.

Results: Of 286 registered neonates, 278 mothers were contacted. Of 105 analyzed maternal samples, two (1.9%) were HPA-1a antigen negative. Antibody analyses revealed in total three (2.9%) mothers with anti-HPA: one mother (0.94%) with anti-HPA-1a and two mothers (1.9%) with anti-HPA-5b, of whom one had concurrent anti-HPA-15a. Twenty-four percent tested positive for anti-HLA Class I antibodies. A total of 8.5% of neonates (5/59) with PLT counts available in clinical records were severely thrombocytopenic, with PLT counts of less than 50 × 10 /L.

Conclusions: This retrospective cohort revealed a wide range of factors associated with ICH in neonates born from 32 weeks of gestation and suggests PLT alloimmunization to be a less common contributor than anticipated.
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http://dx.doi.org/10.1111/trf.14394DOI Listing
January 2018

Antenatal corticosteroid treatment and placental pathology, with a focus on villous maturation.

Acta Obstet Gynecol Scand 2018 Jan 26;97(1):74-81. Epub 2017 Oct 26.

Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.

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 and 26  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.
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http://dx.doi.org/10.1111/aogs.13242DOI Listing
January 2018

Exploring the association between chorangioma and infantile haemangioma in singleton and multiple pregnancies: a case-control study in a Swedish tertiary centre.

BMJ Open 2017 Sep 3;7(9):e015539. Epub 2017 Sep 3.

Section of Perinatal Pathology, Department of Pathology, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Objectives: Placenta or placental chorangioma could be the origin site of infantile haemangioma since they share various histochemical and genetic characteristics with placental vascular tissue. The aim of the current study was to investigate the association between chorangiomas and infantile haemangiomas in singleton and multiple pregnancies.

Materials And Methods: An informative questionnaire enquiring about the presence or not of infantile haemangioma and including illustrative photos of haemangioma was sent to 469 (153 cases with chorangioma and 316 controls) mothers of 323 singleton (104 cases and 219 controls) and 146 multiple (49 cases and 97 controls) liveborn neonates registered in Sweden. Overall, 310 mothers (66.1%) from 216 singleton and 94 multiple pregnancies (96 cases and 214 controls) provided feedback and their consent to participate in the current case-control study.

Results: The incidence of infantile haemangioma showed no statistically significant differences between cases and controls (18.8% vs 18.2%) or between singleton and multiple pregnancies (18.9% vs 17.0%). The frequency of pre-eclampsia was significantly higher in cases with chorangioma compared with controls (41.7% vs 24.3%, OR=2.22, 95% CI 1.33 to 3.71, p=0.0022) and in singleton compared with multiple pregnancies (33.3% vs 21.3%, OR=1.85, 95% CI 1.04 to 3.26, p=0.034), whereas there were no significant differences in the incidence of infantile haemangioma in neonates of mothers with or without pre-eclampsia or in neonates of mothers with multiple compared with singleton pregnancies.

Conclusion: There was no association between placental chorangiomas and infantile haemangiomas. Multiple pregnancies or pre-eclampsia were not significantly related to higher incidence of infantile haemangioma.
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http://dx.doi.org/10.1136/bmjopen-2016-015539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588969PMC
September 2017

Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis.

Front Immunol 2017 11;8:795. Epub 2017 Jul 11.

Translational Cell Therapy Research Group (TCR), Division of Therapeutic Immunology, Department of LabMed, Karolinska Institutet, Stockholm, Sweden.

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) × 10 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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http://dx.doi.org/10.3389/fimmu.2017.00795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504152PMC
July 2017

Composition and functionality of the intrahepatic innate lymphoid cell-compartment in human nonfibrotic and fibrotic livers.

Eur J Immunol 2017 08 11;47(8):1280-1294. Epub 2017 Jul 11.

Center for Infectious Medicine, Department of Medicine, Karolinska Institute Stockholm, Sweden.

Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties, and functionality of ILC1s, ILC2s, and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in nonfibrotic livers as compared with that in mucosal tissues, with NKp44 ILC3s accounting for the majority of total intrahepatic ILCs. The frequency of ILC2s, representing a small fraction of ILCs in nonfibrotic livers, increased in liver fibrosis and correlated directly with the severity of the disease. Notably, intrahepatic ILC2s secreted the profibrotic cytokine IL-13 when exposed to IL-33 and thymic stromal lymphopoetin (TSLP); these cytokines were produced by hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells in response to TLR-3 stimulation. In summary, the present results provide the first detailed characterization of intrahepatic ILCs in human adult and fetal liver. The results indicate a role for ILC2s in human liver fibrosis, implying that targeting ILC2s might be a novel therapeutic strategy for its treatment.
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http://dx.doi.org/10.1002/eji.201646890DOI Listing
August 2017