Publications by authors named "Constantin von Kaisenberg"

88 Publications

The cumulative impact of parity on the body mass index (BMI) in a non-selected Lower Saxony population.

J Perinat Med 2020 Dec 1. Epub 2020 Dec 1.

Department of Obstetrics and Gynecology, Faculty of Medicine, University Medical Center Freiburg, University of Freiburg, Freiburg, Germany.

Objectives: During the last decade obesity has been continuously rising in adults in industrial countries. The increased occurrence of perinatal complications caused by maternal obesity poses a major challenge for obstetricians during pregnancy and childbirth. This study aims to examine the association between parity, pregnancy, birth risks, and body mass index (BMI) of women from Lower Saxony, Germany.

Methods: This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony's statewide quality assurance initiative. Mothers were categorized according to BMI as normal weight (18.5 to <25 kg/m2) or obese (≥30 kg/m2).

Results: Most of the mothers in this study population were either in their first (33.9%) or second pregnancy (43.4%). The mean age of women giving birth for the first time was 28.3 years. Maternal age increased with increasing parity. The proportion of pregnant women with a BMI over 30 was 11% in primiparous women, 14.3% in second para, 17.3% in third para and 24.1% in fourth para or more women. Increasing parity was positively correlated with the incidence of classical diseases related to obesity, namely diabetes mellitus, gestational diabetes, hypertension, pregnancy-related hypertension and urinary protein excretion. An increased risk of primary or secondary cesarean section was observed in the obese women, particularly during the first deliveries.

Conclusions: There is a positive and significant correlation between parity and increased maternal BMI. The highest weight gain happens during the first pregnancy. The rate of operative deliveries and complications during delivery is increased in obese pregnant women.
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http://dx.doi.org/10.1515/jpm-2020-0261DOI Listing
December 2020

PD-1 Blockade Aggravates Epstein-Barr Virus Post-Transplant Lymphoproliferative Disorder in Humanized Mice Resulting in Central Nervous System Involvement and CD4 T Cell Dysregulations.

Front Oncol 2020 12;10:614876. Epub 2021 Jan 12.

Laboratory of Regenerative Immune Therapies Applied, REBIRTH - Research Center for Translational Regenerative Medicine, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies after solid organ or allogeneic stem cell transplantation. Most PTLD cases are B cell neoplasias carrying Epstein-Barr virus (EBV). A therapeutic approach is reduction of immunosuppression to allow T cells to develop and combat EBV. If this is not effective, approaches include immunotherapies such as monoclonal antibodies targeting CD20 and adoptive T cells. Immune checkpoint inhibition (ICI) to treat EBV PTLD was not established clinically due to the risks of organ rejection and graft--host disease. Previously, blockade of the programmed death receptor (PD)-1 by a monoclonal antibody (mAb) during infection of mononuclear cells with the EBV/M81 strain showed lower xenografted lymphoma development in mice. Subsequently, fully humanized mice infected with the EBV/B95-8 strain and treated with a PD-1 blocking mAb showed aggravation of PTLD and lymphoma development. Here, we evaluated in fully humanized mice after EBV/B95-8 or EBV/M81 infections the effects of a clinically used PD-1 blocker. Fifteen to 17 weeks after human CD34 stem cell transplantation, Nod.Rag.Gamma mice were infected with two types of EBV laboratory strains expressing firefly luciferase. Dynamic optical imaging analyses showed systemic EBV infections and this triggered vigorous human CD8 T cell expansion. Pembrolizumab administered from 2 to 5 weeks post-infections significantly aggravated EBV systemic spread and, for the M81 model, significantly increased the mortality of mice. ICI promoted Ki67CD30CD20EBERPD-L1 PTLD with central nervous system (CNS) involvement, mirroring EBV CNS PTLD in humans. PD-1 blockade was associated with lower frequencies of circulating T cells in blood and with a profound collapse of CD4 T cells in lymphatic tissues. Mice treated with pembrolizumab showed an escalation of exhausted T cells expressing TIM-3, and LAG-3 in tissues, higher levels of several human cytokines in plasma and high densities of FoxP3 regulatory CD4 and CD8 T cells in the tumor microenvironment. We conclude that PD-1 blockade during acute EBV infections driving strong CD8 T cell priming decompensates T cell development towards immunosuppression. Given the variety of preclinical models available, our models conferred a cautionary note indicating that PD-1 blockade aggravated the progression of EBV PTLD.
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http://dx.doi.org/10.3389/fonc.2020.614876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837057PMC
January 2021

Pravastatin Promotes Endothelial Colony-Forming Cell Function, Angiogenic Signaling and Protein Expression In Vitro.

J Clin Med 2021 Jan 6;10(2). Epub 2021 Jan 6.

Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.

Endothelial dysfunction is a primary feature of several cardiovascular diseases. Endothelial colony-forming cells (ECFCs) represent a highly proliferative subtype of endothelial progenitor cells (EPCs), which are involved in neovascularization and vascular repair. Statins are known to improve the outcome of cardiovascular diseases via pleiotropic effects. We hypothesized that treatment with the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor pravastatin increases ECFCs' functional capacities and regulates the expression of proteins which modulate endothelial health in a favourable manner. Umbilical cord blood derived ECFCs were incubated with different concentrations of pravastatin with or without mevalonate, a key intermediate in cholesterol synthesis. Functional capacities such as migration, proliferation and tube formation were addressed in corresponding in vitro assays. mRNA and protein levels or phosphorylation of protein kinase B (AKT), endothelial nitric oxide synthase (eNOS), heme oxygenase-1 (HO-1), vascular endothelial growth factor A (VEGF-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and endoglin (Eng) were analyzed by real time PCR or immunoblot, respectively. Proliferation, migration and tube formation of ECFCs were enhanced after pravastatin treatment, and AKT- and eNOS-phosphorylation were augmented. Further, expression levels of HO-1, VEGF-A and PlGF were increased, whereas expression levels of sFlt-1 and Eng were decreased. Pravastatin induced effects were reversible by the addition of mevalonate. Pravastatin induces beneficial effects on ECFC function, angiogenic signaling and protein expression. These effects may contribute to understand the pleiotropic function of statins as well as to provide a promising option to improve ECFCs' condition in cell therapy in order to ameliorate endothelial dysfunction.
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http://dx.doi.org/10.3390/jcm10020183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825508PMC
January 2021

Pregnancy in pulmonary arterial hypertension: Midterm outcomes of mothers and offspring.

J Heart Lung Transplant 2021 Mar 11;40(3):229-233. Epub 2020 Dec 11.

Department of Respiratory Medicine, Hannover Medical School Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center of Lung Research (DZL), Hannover, Germany.

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http://dx.doi.org/10.1016/j.healun.2020.12.002DOI Listing
March 2021

Low Ethanol Concentrations Promote Endothelial Progenitor Cell Capacity and Reparative Function.

Cardiovasc Ther 2020 22;2020:4018478. Epub 2020 Sep 22.

Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.

Background: Endothelial progenitor cells (EPCs) are recruited to injured endothelium and contribute to its regeneration. There is evidence that moderate ethanol consumption prevents the development and progression of atherosclerosis in a variety of and models and increases the mobilization of progenitor cells. Furthermore, there are studies that identified ethanol at low concentration as a therapeutic tool to mobilize progenitor cells in peripheral blood. At the same time, the cell number of EPCs represents a close link to cardiovascular system constitution and function and contributes to cardiovascular risk. The aim of this study was to evaluate the effect of low dose ethanol on typical features of endothelial colony-forming cells (ECFCs), a proliferative subtype of EPCs.

Methods And Results: We tested whether ethanol impacts the functional abilities of ECFC (e.g., migration, tube formation, and proliferation) using assays, the intercommunication of ECFC by exploring cell surface molecules by flow cytometry, and the expression of (anti-)angiogenic molecules by ELISA. Low concentrations of ethanol concentration promoted migration, proliferation, and tubule formation of ECFC. The expression of the cell surface marker VE-cadherin, a protein which plays an important role in cell-cell interaction, was enhanced by ethanol, while (anti-)angiogenic molecule expression was not impacted.

Conclusion: Ethanol at moderate concentrations increases the angiogenic abilities of endothelial progenitor cells thus possibly contributing to vasoprotection.
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http://dx.doi.org/10.1155/2020/4018478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528128PMC
November 2020

Screening, Management and Delivery in Twin Pregnancy.

Ultraschall Med 2020 Oct 5. Epub 2020 Oct 5.

Department of Obstetrics and Fetal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

The following AWMF guideline (DGGG/AGG & DEGUM responsible) deals with the diagnosis, screening and management of twins as well as the timing and mode of birth.Twin pregnancies can be classified as dichorionic diamniotic (DC DA), monochorionic diamniotic (MC DA) and monochorionic monoamniotic (MC MA) which are always monochorionic.Twin pregnancies can be concordant (both twins are affected) or discordant (only one twin is affected) for chromosomal defects, malformations, growth restriction and hemodynamic disorders.Chorionicity is the prognostically most significant parameter. Monochorial twins have significantly higher risks of intrauterine morbidity and mortality compared to dichorial twins.In particular, general aspects of twin pregnancies such as dating, determination of chorionicity and amnionicity, the labeling of twin fetuses and the perinatal switch phenomenon are discussed.Routine monitoring of MC and DC twin pregnancies with ultrasound at 11-13 weeks of gestation for chromosomal defects, invasive prenatal diagnosis, first-trimester NT or CRL discrepancies, early diagnosis of fetal anatomical defects, and management of twins with abnormalities, including selective fetocide, is described.Second trimester screening and management for preterm birth, intrauterine selective growth restriction (sFGR), classification of monochorial twins with sFGR, and management of the surviving twin after the death of the co-twin are described.Complications exclusively affecting MC twins include Twin to Twin Transfusion Syndrome (TTTS) with the important topics screening, prognosis, complications of laser therapy, timing of delivery, risks for brain abnormalities and delayed neurological development, Twin Anemia-Polycythemia Sequence (TAPS) and Twin Reversed Arterial Perfusion (TRAP) Sequence. This also includes MC MA twins as well as conjoined twins.Finally, the birth mode and time for DC and MC twin pregnancies are described.The information is summarized in 62 recommendations for action, 4 tables and 8 illustrations with comprehensive background texts.The guideline is an international guideline adaptation (ISUOG, NICE) as well as a systematic literature search and is up-to-date.
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http://dx.doi.org/10.1055/a-1248-8896DOI Listing
October 2020

Current Approach for External Cephalic Version in Germany.

Geburtshilfe Frauenheilkd 2020 Oct 25;80(10):1041-1047. Epub 2020 Sep 25.

Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Hochschule Hannover, Hannover, Germany.

Fetal breech presentation at terms occurs in 3 - 6% of pregnancies. External cephalic version can reduce the number of cesarean sections and vaginal breech deliveries. Different approaches are used to carry out external cephalic version. This study looked at the different approaches used in Germany and compared the approach used with the recommendations given in German and international guidelines. An anonymized online survey of 234 hospitals in Germany was carried out in 2018. In addition to asking about hospital structures, questions also focused on how external version was carried out in practice (preparations, tocolysis, anesthetics, etc.), on relative and absolute contraindications and on the success rate. 37.2% of the hospitals approached for the survey participated in the study. Of these, 98.8% performed external version procedures. The majority of participating hospitals were university hospitals (26.4%) and maximum care hospitals (35.6%) with an average number of more than 2000 births per year (60.9%). External cephalic version is the preferred (61.7%) obstetrical procedure to deal with breech presentation, rather than vaginal breech birth or primary cesarean section. 45.8% of respondents carry out external version procedures on an outpatient basis, and 42.1% of hospitals perform the procedure as an inpatient intervention, especially from the 37th week of gestation. Prior to performing an external version procedure, 21.6% of surveyed institutions carry out a vaginal examination to evaluate possible fixation of the fetal rump. 95.5% of institutions used fenoterol for tocolytic therapy; the majority using it for continuous tocolysis (70.2%). 1 - 3 attempts at external version (8.4%) were usually carried out by a specific senior physician. In most cases, no analgesics were administered. The reported rate of emergency cesarean sections was very low. The most common indication for emergency C-section was pathological CTG (56,7%). The assessment of relative and absolute contraindications varied, depending on the surveyed hospital. 67.5% asked patients to empty their bladders before carrying out external version, while 10.8% carried out external version when the bladder was filled. The reported success rate was more than 45%. After successful version, only 14.8% of hospitals arranged for patients to wear an abdominal binder. For 32.4%, the decision to apply an abdominal binder was taken on a case-by-case basis. The approach used in Germany to carry out external cephalic version is based on the (expired) German guideline on breech presentation. Based on the evidence obtained, a number of individual recommendations should be re-evaluated. More recent international guidelines could be useful to update the standard procedure.
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http://dx.doi.org/10.1055/a-1127-8646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518935PMC
October 2020

CAR-T Cells Targeting Epstein-Barr Virus gp350 Validated in a Humanized Mouse Model of EBV Infection and Lymphoproliferative Disease.

Mol Ther Oncolytics 2020 Sep 8;18:504-524. Epub 2020 Aug 8.

Laboratory of Regenerative Immune Therapies Applied, Hannover Medical School, 30625 Hannover, Germany.

Epstein-Barr virus (EBV) is a latent and oncogenic human herpesvirus. Lytic viral protein expression plays an important role in EBV-associated malignancies. The EBV envelope glycoprotein 350 (gp350) is expressed abundantly during EBV lytic reactivation and sporadically on the surface of latently infected cells. Here we tested T cells expressing gp350-specific chimeric antigen receptors (CARs) containing scFvs derived from two novel gp350-binding, highly neutralizing monoclonal antibodies. The scFvs were fused to CD28/CD3ζ signaling domains in a retroviral vector. The produced gp350CAR-T cells specifically recognized and killed gp350 293T cells . The best-performing 7A1-gp350CAR-T cells were cytotoxic against the EBV B95-8 cell line, showing selectivity against gp350 cells. Fully humanized Nod.Rag.Gamma mice transplanted with cord blood CD34 cells and infected with the EBV/M81/fLuc lytic strain were monitored dynamically for viral spread. Infected mice recapitulated EBV-induced lymphoproliferation, tumor development, and systemic inflammation. We tested adoptive transfer of autologous CD8gp350CAR-T cells administered protectively or therapeutically. After gp350CAR-T cell therapy, 75% of mice controlled or reduced EBV spread and showed lower frequencies of EBER B cell malignant lymphoproliferation, lack of tumor development, and reduced inflammation. In summary, CD8gp350CAR-T cells showed proof-of-concept preclinical efficacy against impending EBV lymphoproliferation and lymphomagenesis.
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http://dx.doi.org/10.1016/j.omto.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479496PMC
September 2020

Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.

PLoS Pathog 2020 07 15;16(7):e1008560. Epub 2020 Jul 15.

Clinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

Human cytomegalovirus (HCMV) causes serious complications to immune compromised hosts. Dendritic cells (iDCgB) expressing granulocyte-macrophage colony-stimulating factor, interferon-alpha and HCMV-gB were developed to promote de novo antiviral adaptive responses. Mice reconstituted with a human immune system (HIS) were immunized with iDCgB and challenged with HCMV, resulting into 93% protection. Immunization stimulated the expansion of functional effector memory CD8+ and CD4+ T cells recognizing gB. Machine learning analyses confirmed bone marrow T/CD4+, liver B/IgA+ and spleen B/IgG+ cells as predictive biomarkers of immunization (≈87% accuracy). CD8+ and CD4+ T cell responses against gB were validated. Splenic gB-binding IgM-/IgG+ B cells were sorted and analyzed at a single cell level. iDCgB immunizations elicited human-like IgG responses with a broad usage of various IgG heavy chain V gene segments harboring variable levels of somatic hypermutation. From this search, two gB-binding human monoclonal IgGs were generated that neutralized HCMV infection in vitro. Passive immunization with these antibodies provided proof-of-concept evidence of protection against HCMV infection. This HIS/HCMV in vivo model system supported the validation of novel active and passive immune therapies for future clinical translation.
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http://dx.doi.org/10.1371/journal.ppat.1008560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363084PMC
July 2020

Transfer of an interprofessional emergency caesarean section training program: using questionnaire combined with outcome data of newborn.

Arch Gynecol Obstet 2020 09 13;302(3):585-593. Epub 2020 Jul 13.

Department of Obstetrics and Gynecology, Hannover Medical School, Hannover Medical School, Carl-Neuberg-Str. 1Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Puprose: An emergency caesarean section is a potentially life-threatening situation both for the mother and the newborn. Non-technical skills can be improved by simulation training and are necessary to manage this urgent situation successfully. The objective of this study was to investigate, if training of emergency caesarean section can be transferred into daily work to improve the outcome parameters pH an APGAR of the newborn.

Methods: In this pre-post study, 141 professionals took part in a training for emergency caesarean section. Participants received a questionnaire, based on the tools "Training Evaluation Inventory" and "Transfer Climate Questionnaire" 1 year after training. Outcome data of the newborn were collected from the hospitals information system.

Results: Except the scale "extinction", Cronbach's alpha was higher than 0.62. All scales were rated lower than 2.02 on a 5-point Likert Scale (1 = fullest approval; 5 = complete rejection). "Negative reinforcement" was rated with 2.87 (SD 0.73). There were no significant differences in outcome data prior. The questionnaire fulfils criteria for application except the scale "extinction".

Conclusion: The presented training course was perceived as useful by the professionals and attitudes toward training were positive; the content was positively reinforced in practice 1 year after training. Parameters of the newborn did not change. It is conceivable that other outcome parameters (e.g. posttraumatic stress disorder) are addressed by the training. The development of relevant outcome parameters for the quality of emergency sections needs further investigation.
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http://dx.doi.org/10.1007/s00404-020-05617-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447674PMC
September 2020

[Kidney Cysts and Cystic Nephropathies in Children - A Consensus Guideline by 10 German Medical Societies].

Klin Padiatr 2020 Sep 13;232(5):228-248. Epub 2020 Jul 13.

Center for Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg.

This consensus-based guideline was developed by all relevant German pediatric medical societies. Ultrasound is the standard imaging modality for pre- and postnatal kidney cysts and should also exclude extrarenal manifestations in the abdomen and internal genital organs. MRI has selected indications. Suspicion of a cystic kidney disease should prompt consultation of a pediatric nephrologist. Prenatal management must be tailored to very different degrees of disease severity. After renal oligohydramnios, we recommend delivery in a perinatal center. Neonates should not be denied renal replacement therapy solely because of their age. Children with unilateral multicystic dysplastic kidney do not require routine further imaging or nephrectomy, but long-term nephrology follow-up (as do children with uni- or bilateral kidney hypo-/dysplasia with cysts). ARPKD (autosomal recessive polycystic kidney disease), nephronophthisis, Bardet-Biedl syndrome and HNF1B mutations cause relevant extrarenal disease and genetic testing is advisable. Children with tuberous sclerosis complex, tumor predisposition (e. g. von Hippel Lindau syndrome) or high risk of acquired kidney cysts should have regular ultrasounds. Even asymptomatic children of parents with ADPKD (autosomal dominant PKD) should be monitored for hypertension and proteinuria. Presymptomatic diagnostic ultrasound or genetic examination for ADPKD in minors should only be done after thorough counselling. Simple cysts are very rare in children and ADPKD in a parent should be excluded. Complex renal cysts require further investigation.
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http://dx.doi.org/10.1055/a-1179-0728DOI Listing
September 2020

Repeated Freezing Procedures Preserve Structural and Functional Properties of Amniotic Membrane for Application in Ophthalmology.

Int J Mol Sci 2020 Jun 4;21(11). Epub 2020 Jun 4.

Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, Germany.

For decades, the unique regenerative properties of the human amniotic membrane (hAM) have been successfully utilized in ophthalmology. As a directly applied biomaterial, the hAM should be available in a ready to use manner in clinical settings. However, an extended period of time is obligatory for performing quality and safety tests. Hence, the low temperature storage of the hAM is a virtually inevitable step in the chain from donor retrieval to patient application. At the same time, the impact of subzero temperatures carries an increased risk of irreversible alterations of the structure and composition of biological objects. In the present study, we performed a comprehensive analysis of the hAM as a medicinal product; this is intended for a novel strategy of application in ophthalmology requiring a GMP production protocol including double freezing-thawing cycles. We compared clinically relevant parameters, such as levels of growth factors and extracellular matrix proteins content, morphology, ultrastructure and mechanical properties, before and after one and two freezing cycles. It was found that epidermal growth factor (EGF), transforming growth factor beta 1 (TGF-β1), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), hyaluronic acid, and laminin could be detected in all studied conditions without significant differences. Additionally, histological and ultrastructure analysis, as well as transparency and mechanical tests, demonstrated that properties of the hAM required to support therapeutic efficacy in ophthalmology are not impaired by dual freezing.
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http://dx.doi.org/10.3390/ijms21114029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312941PMC
June 2020

Intracranial emergencies during pregnancy requiring urgent neurosurgical treatment.

Clin Neurol Neurosurg 2020 Aug 12;195:105905. Epub 2020 May 12.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Objective: Despite contemporary diagnostic and therapeutic techniques intracranial emergencies in the obstetric setting pose still a major challenge for the clinicians. There are limited guidelines and differing ethical views. Multidisciplinary teams are needed to support the pregnant woman in a way that she can deliver a viable and healthy child. The aim of the present study was to scrutinize the management of intracranial emergencies during pregnancy which needed urgent neurosurgical treatment.

Patients And Methods: Data of all pregnant women who presented with newly diagnosed intracranial pathologies and neurological symptoms caused by these pathologies in an emergency setting were collected over a 10-year period (2008-2018). Patient characteristics including maternal age, gestational age, and preoperative work-up of both mother and fetus were recorded. Furthermore, the surgical treatment, mode of delivery, and neonatal and maternal outcomes were analysed.

Results: The mean maternal age was 32.7 years and most patients were in their third trimester. There was one twin pregnancy (total of 12 fetuses). Five out of eleven pregnant women suffered from intracerebral haemorrhage (epidural haematoma (1), arteriovenous malformation (1), subarachnoid haemorrhage (2) and intracerebral haemorrhage (1)) and the other six patients had intracranial neoplasms (primary meningeal sarcoma (1), trigeminal schwannoma (1), anaplastic astrocytoma (2), glioblastoma (1) and sphenoid wing meningioma (1)).Neurosurgical procedures were performed via craniotomies in eight patients. A stereotactic biopsy via a frontal burr hole was achieved one patient. The two other patients with subarachnoid haemorrhage due to rupture of PICA aneurysms were treated with coil embolization. Depending on the gestational age and the clinical condition of the pregnant women it was decided to perform an emergency Caesarean section prior to further therapeutic measures in seven patients. Two out of 12 fetuses were unviable. Six women survived, while five women succumbed to the intracranial pathology.

Conclusion: The individualized treatment approach in this peculiar obstetric scenario needs to consider various issues such as the clinical condition of the pregnant woman, prognosis of the disease, gestational age and the status of the pregnancy. The primary concern in this context must be the mother`s health and safety. Caesarean section is the primary mode of delivery in most cases. While contemporary care can insure survival for the majority of infants, maternal mortality still poses an extraordinary challenge. Interdisciplinary consulting of the patient and/or her family is necessary to develop a treatment strategy for both the expectant woman and her offspring.
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http://dx.doi.org/10.1016/j.clineuro.2020.105905DOI Listing
August 2020

Spinal Emergency Surgery During Pregnancy: Contemporary Strategies and Outcome.

World Neurosurg 2020 07 16;139:e421-e427. Epub 2020 Apr 16.

Department of Neurosurgery, Hannover Medical School, Hannover, Germany.

Background: Low back pain is a common complaint during pregnancy. However, spinal pathologies, which manifest with severe pain, radiculopathy, and acute neurologic deficits because of disk herniation or mass lesions require special attention. Here, we present our interdisciplinary experience in the surgical management of spinal emergencies during pregnancy.

Methods: The data of pregnant women who underwent surgery for spinal pathologies over a 10-year period were collected. Patient-related characteristics such as maternal age, gestational age, preoperative workup, signs and symptoms of mothers, and diagnostic procedures were evaluated. After an interdisciplinary conference, individualized treatment plans regarding available options were developed. Fetal Doppler and cardiotocography were obtained before and after surgery.

Results: Nine pregnant women presented with spinal disorders and underwent spinal emergency surgery within the study period. The mean maternal age was 32.2 years. Six women presented with lumbar disk herniations manifesting as severe sciatica or foot drop and 3 patients had thoracic mass lesions resulting in cauda equine syndrome and/or ataxia. The mean gestational age at the time of presentation was 26.5 weeks. Caesarean sections were performed in 3 women prior to the neurosurgical procedure, whereas the pregnancies were maintained in the 6 other patients. Eight infants who were healthy at birth had an unremarkable development.

Conclusions: Surgery for spinal emergencies in pregnancy can be performed safely according to individual treatment plans developed by an interdisciplinary team taking into account the expectant mother's decision. Maintenance of pregnancy is possible and feasible in most patients.
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http://dx.doi.org/10.1016/j.wneu.2020.04.019DOI Listing
July 2020

TCR repertoire analysis reveals phosphoantigen-induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults.

J Leukoc Biol 2020 06 17;107(6):1023-1032. Epub 2020 Feb 17.

Institute of Immunology, Hannover Medical School, Hannover, Germany.

The Vγ9Vδ2 T cell subset is the major γδ T cell subset in human peripheral blood and has the unique ability to contribute to immune surveillance by detecting pyrophosphorylated metabolites of isoprenoid synthesis, termed phosphoantigens (pAgs). Vγ9Vδ2 T cells are first detected at midgestation and show postnatal expansion. Interestingly, neonatal Vγ9Vδ2 T cells display a higher TCR repertoire diversity with more public clonotypes and lower pAg responsiveness than in adults. Notably, it is not known whether postnatal changes occur by TCR-dependent reactivity to pAg exposure. Here, we applied next-generation sequencing of γδ TCR repertoires to understand potential differences in the pAg-mediated response of neonatal and adult Vγ9Vδ2 T cells at the level of the expressed γδ TCR. We observed a polyclonal pAg-induced response of neonatal and adult Vγ9Vδ2 T cells, albeit neonatal γδ T cells showed less in vitro pAg responsiveness. Neonatal Vγ9Vδ2 T cells displayed a less pronounced bias for Jδ1 usage and a more frequent use of Jδ2 or Jδ3 that remained stable after pAg exposure. In addition, public and private Vδ2 TRD clones took part in the polyclonal pAg-induced response in neonates and adults. In conclusion, adult and neonatal Vγ9Vδ2 T cells both undergo polyclonal pAg-induced proliferation, whereas especially adult Vγ9Vδ2 T cells display a high stability at the level of the expressed TCR repertoire.
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http://dx.doi.org/10.1002/JLB.1MA0120-427RRDOI Listing
June 2020

Evaluation of folate concentration in amniotic fluid and maternal and umbilical cord blood during labor.

Arch Med Sci 2019 Oct 8;15(6):1425-1432. Epub 2018 Oct 8.

Food, Nutrition and Health Program, Faculty of Land and Food Systems, The University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: Folate is required for fetal, placental and maternal tissue growth during pregnancy. A decline in maternal circulating folate concentrations and an increase in total homocysteine (a non-specific indicator of folate deficiency) have been observed with the progression of pregnancy. However, the role of folate in the third trimester of pregnancy is not clear and folate status in late pregnancy has not so far been widely analyzed. The main aim of this retrospective cross-sectional study was to determine the folate concentrations in amniotic fluid and in maternal and umbilical cord blood serum derived during delivery.

Material And Methods: This study was conducted on 175 pregnant Polish women (white/Caucasian) aged between 17 and 42 years. Only pregnancies without birth defects were included in this study. Amniotic fluid, maternal serum, and umbilical cord blood samples were collected during vaginal delivery or cesarean section. Folate concentration was determined using a microbiological assay.

Results: Strong correlations were observed between the concentrations of folate in amniotic fluid and maternal serum (rho = 0.67, < 0.001) and amniotic fluid and cord blood serum (rho = 0.49, < 0.001) and between maternal serum and cord blood serum (rho = 0.67, < 0.001). Folate concentrations in amniotic fluid were significantly associated with maternal age (rho = 0.19, < 0.05). Pre-pregnancy body mass index and maternal weight/neonatal birth weight ratio were independent predictors of folate concentrations in maternal serum (β = 0.33, < 0.05; β = -0.19, < 0.05) and amniotic fluid (β = 0.28, < 0.05; β = -0.19, < 0.05) in late pregnancy.

Conclusions: Folate concentrations in amniotic fluid are associated with maternal and neonatal folate status peripartum in healthy women.
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http://dx.doi.org/10.5114/aoms.2018.78776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855149PMC
October 2019

Maternal Overweight, Inflammation and Neurological Consequences for the Preterm Child: Results of the ELGAN Study.

Geburtshilfe Frauenheilkd 2019 Nov 11;79(11):1176-1182. Epub 2019 Nov 11.

Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany.

Maternal overweight and obesity are prenatal risk factors for obstetrical complications, preterm birth, neonatal morbidity as well as cognitive and behavioural developmental disorders in children. Paediatric morbidity and mortality as well as child development disorders are significantly associated with maternal obesity. Particularly in the neurodevelopmental and psychiatric area, it is becoming increasingly clear that, in children of mothers with an increased body mass index (BMI), there is a high correlation with childhood cognitive disabilities, attention disorders, and diseases on the autistic spectrum. The ELGAN (Extremely Low Gestational Age Newborn) study is a multicentre study which has been supported since 2000 by the National Institutes of Health (NIH) and whose objective is to research predictors for neonatal brain damage and neurological-cognitive sequelae in premature infants. The areas of focus are the connection between maternal overweight and obesity and pregnancy complications, APGAR scores and systemic inflammatory markers. In this overview, our aim is to summarise the work in this area and discuss it critically on the basis of current literature. We will examine the hypothesis whether maternal overweight and obesity in terms of a chronic inflammatory state is associated with neonatal inflammation which in turn is associated with an unfavourable development prognosis.
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http://dx.doi.org/10.1055/a-0960-0939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6846733PMC
November 2019

Dual Pharmacological Inhibition of Angiopoietin-2 and VEGF-A in Murine Experimental Sepsis.

J Vasc Res 2020 14;57(1):34-45. Epub 2019 Nov 14.

Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany,

Background: Sepsis is a pathological host response to infection leading to vascular barrier breakdown due to elevated levels of angiopoietin-2 (Angpt-2) and vascular endothelial growth factor-A (VEGF-A). Here, we tested a novel heterodimeric bispecific monoclonal IgG1-cross antibody of Angpt-2 and VEGF - termed "A2V."

Methods: Cecal ligation and puncture was used to induce murine polymicrobial sepsis. Organs and blood were harvested for fluorescence immunohistochemistry and RT-PCR, and survival was recorded. In vitro endothelial cells were stimulated with plasma from septic shock patients costimulated with A2V or IgG antibody followed by immunocytochemistry and real-time transendothelial electrical resistance.

Results: Septic mice treated with A2V had a reduced induction of the endothelial adhesion molecule ICAM-1, leading to a trend towards less transmigration of inflammatory cells (A2V: 42.2 ± 1.0 vs. IgG 48.5 ± 1.7 Gr-1+ cells/HPF, p = 0.08) and reduced tissue levels of inflammatory cytokines (e.g., IL-6 mRNA: A2V 9.4 ± 3.2 vs. IgG 83.9 ± 36.7-fold over control, p = 0.03). Endothelial permeability was improved in vivo and in vitro in stimulated endothelial cells with septic plasma. Survival was improved by 38% (p = 0.02).

Conclusion: Dual inhibition of Angpt-2 and VEGF-A improves murine sepsis morbidity and mortality, making it a potential therapeutic against vascular barrier breakdown.
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http://dx.doi.org/10.1159/000503787DOI Listing
September 2020

Umbilical cord as a long-term source of activatable mesenchymal stromal cells for immunomodulation.

Stem Cell Res Ther 2019 09 23;10(1):285. Epub 2019 Sep 23.

Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.

Background: Mesenchymal stromal cells (MSCs) are used in over 800 clinical trials mainly due to their immune inhibitory activity. Umbilical cord (UC), the second leading source of clinically used MSCs, is usually cut in small tissue pieces. Subsequent cultivation leads to a continuous outgrowth of MSC explant monolayers (MSC-EMs) for months. Currently, the first MSC-EM culture takes approximately 2 weeks to grow out, which is then expanded and applied to patients. The initiating tissue pieces are then discarded. However, when UC pieces are transferred to new culture dishes, MSC-EMs continue to grow out. In case the functional integrity of these cells is maintained, later induced cultures could also be expanded and used for cell therapy. This would drastically increase the number of available cells for each patient. To test the functionality of MSC-EMs from early and late induction time points, we compared the first cultures to those initiated after 2 months by investigating their clonality and immunomodulatory capacity.

Methods: We analyzed the clonal composition of MSC-EM cultures by umbilical cord piece transduction using integrating lentiviral vectors harboring genetic barcodes assessed by high-throughput sequencing. We investigated the transcriptome of these cultures by microarrays. Finally, the secretome was analyzed by multiplexed ELISAs, in vitro assays, and in vivo in mice.

Results: DNA barcode analysis showed polyclonal MSC-EMs even after months of induction cycles. A transcriptome and secretome analyses of early and late MSC cultures showed only minor changes over time. However, upon activation with TNF-α and IFN-γ, cells from both induction time points produced a multitude of immunomodulatory cytokines. Interestingly, the later induced MSC-EMs produced higher amounts of cytokines. To test whether the different cytokine levels were in a therapeutically relevant range, we used conditioned medium (CM) in an in vitro MLR and an in vivo killing assay. CM from late induced MSC-EMs was at least as immune inhibitory as CM from early induced MSC-EMs.

Conclusion: Human umbilical cord maintains a microenvironment for the long-term induction of polyclonal and immune inhibitory active MSCs for months. Thus, our results would offer the possibility to drastically increase the number of therapeutically applicable MSCs for a substantial amount of patients.
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http://dx.doi.org/10.1186/s13287-019-1376-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755709PMC
September 2019

Cytokine Selection of MSC Clones with Different Functionality.

Stem Cell Reports 2019 08 11;13(2):262-273. Epub 2019 Jul 11.

Institute of Experimental Hematology, Hannover Medical School, Building J11, Level 01, Room 6540, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany. Electronic address:

Mesenchymal stromal cells (MSCs) are used in many clinical applications. However, ex vivo expansion is required to reach clinically relevant cell numbers, which might lead to selection of clones with different characteristics. To follow clonal selection, we transduced MSC progenitors in umbilical cord pieces (UCPs) with vectors encoding fluorescent proteins and genetic barcodes. After marked MSC cultures grew out from UCPs, we investigated the influence of cytokines on MSC functionality. Specific cytokine conditions selected for clones from common progenitors. MSC secretome analyses revealed differences dependent on the culture conditions used. Clones expanded in human serum containing culture medium secreted a plethora of growth factors. When expanded in the same medium containing TGF-β, MSCs secreted negligible amounts of cytokines but at the same time led to an increased human chimerism after hematopoietic stem cell transplantation into immunodeficient mice. Our results suggest a major influence of cytokine additives on MSC functionality.
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http://dx.doi.org/10.1016/j.stemcr.2019.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700478PMC
August 2019

Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

FASEB J 2019 10 29;33(10):10633-10647. Epub 2019 Jun 29.

Department of Pediatric Pneumology, Allergology, and Neonatology, Hannover Medical School, Hannover, Germany.

Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Völlger, L., Willers, M., Richter, M., Böhne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Förster, R., von Köckritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.
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http://dx.doi.org/10.1096/fj.201900796RDOI Listing
October 2019

Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells.

FASEB J 2019 08 14;33(8):9142-9153. Epub 2019 May 14.

Gynecology Research Unit, Hannover Medical School, Hannover, Germany.

Endothelial colony-forming cells (ECFCs), a proliferative subpopulation of endothelial progenitor cells, are involved in angiogenesis and endothelial repair. In this study, we investigated endothelial barrier characteristics of ECFCs, whether vitamin D supports cell-cell adhesion and barrier integrity, and how it affects ECFC mobilization and actin dynamics. Although ECFC barrier was disrupted under inflammatory conditions, this effect was rescued by vitamin D treatment, leading to higher stability of an ECFC monolayer. Furthermore, vitamin D enhanced ECFC mobilization toward directional migration. In addition, immunocytochemistry, quantitative real-time PCR, and immunoblotting analysis showed that vitamin D increased endothelial interconnections through vascular endothelial cadherin (VE-cadherin) junctions and by impacting cell dynamics through cofilin and VE-cadherin phosphorylation. Our results suggest that vitamin D treatment efficiently counteracts inflammation in an ECFC monolayer, resulting in higher ECFC barrier integrity. This study provides evidence of a new beneficial effect of vitamin D for ECFC homeostasis.-Schröder-Heurich, B., von Hardenberg, S., Brodowski, L., Kipke, B., Meyer, N., Borns, K., von Kaisenberg, C. S., Brinkmann, H., Claus, P., von Versen-Höynck, F. Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells.
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http://dx.doi.org/10.1096/fj.201802750RRDOI Listing
August 2019

Identification of placental genes linked to selective intrauterine growth restriction (IUGR) in dichorionic twin pregnancies: gene expression profiling study.

Hum Genet 2019 Jun 30;138(6):649-659. Epub 2019 Apr 30.

Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital-Research Institute in Lodz, Lodz, Poland.

A linkage of dichorionic (DC) twin pregnancies with selective intrauterine growth restriction (IUGR) to alterations in placental gene expression is unclear. The aim of the study was to identify placental genes related to hypoxia, adipogenesis and human growth which may contribute to IUGR development. The study group (IUGR/AGA) comprised dichorionic (DC) twin pregnancies, where the weight of the twins differed by > 15%; in addition, one twin was small for gestational age (< 10th percentile-SGA) (IUGR) while the other was appropriate for gestational age (> 10th percentile-AGA). In the control group (AGA/AGA), both fetuses were AGA and their weights differed by < 15%. In the first step (selection), placental expression of 260 genes was analysed by commercial PCR profiler array or qPCR primer assay between six pairs of IUGR/AGA twins. In the second stage (verification), the expression of 20 genes with fold change (FC) > 1.5 selected from the first stage was investigated for 75 DC pregnancies: 23 IUGR/AGA vs. 52 AGA/AGA. The expression of Angiopoetin 2, Leptin and Kruppel-like factor 4 was significantly higher, and Glis Family Zinc Finger 3 was lower, in placentas of SGA fetuses (FC = 3.3; 4.4; 1.6; and - 1.8, respectively; p < 0.05). The dysregulation of gene expression related to angiogenesis and growth factors in placentas of twins born from IUGR/AGA pregnancies suggest that these alternations might represent biological fetal adaptation to the uteral condition. Moreover, DC twin pregnancies may be a good model to identify the differences in placental gene expression between SGA and AGA fetuses.
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http://dx.doi.org/10.1007/s00439-019-02016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554264PMC
June 2019

Impact of maternal education on the outcome of newborns requiring surgery for congenital malformations.

PLoS One 2019 8;14(4):e0214967. Epub 2019 Apr 8.

Department of Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

Objective: Numerous studies established a link between socioeconomic status (SES) and several dimensions of general health. This study examines the association between maternal education as a widely used indicator of SES and outcome in newborns requiring surgical correction of congenital anomalies.

Methods: Ambispective data analysis of newborns with esophageal atresia (EA), intestinal atresia (IA), congenital diaphragmatic hernia (CDH), omphalocele (OC), gastroschisis (GS) undergoing surgery between 01/2008-11/2017 accessing the clinical databases Neodat and Viewpoint. Maternal education was determined according to the validated education classification CASMIN and stratified into "low" SES and "high" SES group. Endpoints were incidence of postoperative complications, length of mechanical ventilation, and readmission to NICU.

Results: Inclusion of 169 patients with EA (n = 32), IA (n = 24), CDH (n = 47), OC (n = 19), GS (n = 47). Women of low SES (n = 67, 40%) attended fewer prenatal screenings (total, 4.6 vs. 7.9, P<0.0001; EA, 3.7 vs. 7.1, P = 0.0002; IA, 3.5 vs. 9.4, P = 0.0006; OC, 2.5 vs. 8.8, P = 0.009; GS, 4.1 vs. 7.0, P = 0.002). Low SES was associated with higher incidence of patients born small for gestational age (37% vs. 20%, P = 0.019), with additional congenital malformations (37% vs. 15%, P = 0.001), being born in a peripheral center (7% vs. 0%, P = 0.008), and with higher incidence of 5´APGAR scores <7 (23% vs. 7%, P = 0.004). Moreover, low SES was associated with higher incidence of postoperative complications (total 70% vs. 32%, P<0.0001; EA, 60% vs. 23%, P = 0.04; IA, 67% vs. 11%, P = 0.008; CDH, 83% vs. 46%, P = 0.009; GS, 74% vs. 25%, P = 0.001), and higher readmission rate to NICU (IA, 33% vs. 0%, P = 0.043; GS, 32% vs. 4%, P = 0.007).

Conclusions: Low maternal education is associated with a reduced uptake of prenatal screenings, adverse neonatal outcomes, and higher incidence of postoperative complications in newborns with congenital anomalies. Primary prevention and specific support should be provided prenatally for families with low SES to avoid adverse outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214967PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453467PMC
December 2019

Preeclampsia-Associated Alteration of DNA Methylation in Fetal Endothelial Progenitor Cells.

Front Cell Dev Biol 2019 19;7:32. Epub 2019 Mar 19.

Department of Obstetrics and Gynecology, Hannover Medical School, Hanover, Germany.

Objective: The pregnancy complication preeclampsia represents an independent risk factor for cardiovascular disease. Our previous research shows a diminished function of fetal endothelial colony-forming cells (ECFC), a proliferative subgroup of endothelial progenitor cells (EPC) in preeclampsia. The aim of this study was to further investigate whether DNA methylation of fetal EPC is affected in preeclampsia.

Methods: The genomic methylation pattern of fetal ECFC from uncomplicated and preeclamptic pregnancies was compared for 865918 CpG sites, and genes were classified into gene networks. Low and advanced cell culture passages were compared to explore whether expansion of fetal ECFC in cell culture leads to changes in global methylation status and if methylation characteristics in preeclampsia are maintained with increasing passage.

Results: A differential methylation pattern of fetal ECFC from preeclampsia compared to uncomplicated pregnancy was detected for a total of 1266 CpG sites in passage 3, and for 2362 sites in passage 5. Key features of primary networks implicated by methylation differences included cell metabolism, cell cycle and transcription and, more specifically, genes involved in cell-cell interaction and Wnt signaling. We identified an overlap between differentially regulated pathways in preeclampsia and cardiovascular system development and function. Cell culture passages 3 and 5 showed similar gene network profiles, and 1260 out of 1266 preeclampsia-associated methylation changes detected in passage 3 were confirmed in passage 5.

Conclusion: Methylation modification caused by preeclampsia is stable and detectable even in higher cell culture passages. An epigenetically modified endothelial precursor may influence both normal morphogenesis and postnatal vascular repair capacity. Further studies on epigenetic modifications in complicated pregnancies are needed to facilitate development of EPC based therapies for cardiovascular alterations.
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http://dx.doi.org/10.3389/fcell.2019.00032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436196PMC
March 2019

Relationship between pre-pregnancy body mass index and mineral concentrations in serum and amniotic fluid in pregnant women during labor.

J Trace Elem Med Biol 2019 Mar 14;52:136-142. Epub 2018 Dec 14.

Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, ul. Wojska Polskiego 31, 60-624 Poznań, Poland. Electronic address:

The aim of the study was to determine the correlations between body mass index (BMI) values before pregnancy and the concentrations of selected elements (Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al, Mn, V, Fe) in blood serum and amniotic fluid (AF) in pregnant women. Elemental analysis of serum and amniotic fluid in 225 Polish women (Caucasian/white) showed a relationship between the concentration of minerals in the above-mentioned samples and the pre-pregnancy BMI. Analysis of blood serum was performed by using ICP-MS and it demonstrated that iron concentration was significantly lower in overweight and obese women. Being underweight in pregnant women was associated with a significantly lower concentration of magnesium and cobalt in the blood serum. Both underweight and overweight women were associated with significantly lower concentrations of calcium and strontium in the blood serum. The concentration of cobalt was significantly higher in underweight women. The concentration of lead in the blood serum of overweight and obese women was significantly higher than in other groups. Analysis of the AF showed that the concentration of copper was significantly lower in overweight and obese women, and the concentration of manganese and vanadium significantly higher than in other groups of women. A deficiency in essential minerals and an excess of heavy metals in women may be associated with abnormal body weight and this is important in the etiopathogenesis of pregnancy and fetal development disorders.
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http://dx.doi.org/10.1016/j.jtemb.2018.12.007DOI Listing
March 2019

Associations between the Level of Trace Elements and Minerals and Folate in Maternal Serum and Amniotic Fluid and Congenital Abnormalities.

Nutrients 2019 Feb 3;11(2). Epub 2019 Feb 3.

Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Poznan, Poland, ul. Wojska Polskiego 31, 60-624 Poznan, Poland.

Congenital birth defects may result in a critical condition affecting the baby, including severe fetal/neonatal handicap and mortality. Several studies have shown that genetic, nutritional, and environmental factors may have an impact on fetal development and neonatal health. The relevance of essential and toxic elements on fetal development has not yet been fully investigated, and the results of recent research indicate that these elements may be crucial in the assessment of the risk of malformations in neonates. We determined the association between essential and toxic elements and the level of folate in maternal serum (MS) and amniotic fluid (AF), along with neonatal abnormalities. A total of 258 pregnant Polish women in the age group of 17⁻42 years participated in this study. AF and MS were collected during vaginal delivery or during cesarean section. An inductively coupled plasma mass spectrometry technique was used to determine the levels of various elements in AF and MS. The results of this exploratory study indicate that the levels of essential and toxic elements are associated with fetal and newborn anatomical abnormalities and growth disorders.
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http://dx.doi.org/10.3390/nu11020328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413094PMC
February 2019