Search

Copyright of Die Nephrologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The fertility of female kidney transplant recipients is increasing with the progression of transplant management. This article aims to evaluate the clinical prognosis of mothers and newborns for post-kidney transplant couples Methods: From January 2019 to April 2022, a total of four couples, all kidney transplant recipients, were successfully prepared for pregnancy after a rigorous preconception evaluation, including three cases of natural conception and one case of in vitro fertilization. Data regarding the mother and newborn, including general clinical condition and laboratory results, were recorded and assessed throughout the pregnancy and up until 12 months after delivery Results: The mean conception age of the mothers was 34.8 years (30-38 years), and the mean interval between renal transplantation and pregnancy was 6.6 years (3.7-8.7 years). All deliveries were by cesarean section and took place without incident. There were three premature births (<37 weeks; average 35.1 weeks). In case 1 (in vitro fertilization), pre-eclampsia occurred during maternity, and this was the only case in which the fetal weight was less than 2,500 g (average 2,576.7 g). The mean Apgar score (1 min) was 7.8 (6-9) and reached 9 in all cases at 5 min. The mothers' eGFR rose during mid-gestation, decreased in late pregnancy, and was largely restored along with proteinuria 1 year postpartum. Postnatal evaluation at 6 months showed normal neurological development. In addition, NK cell and IFN-g levels increased and Treg cell and IL-10 levels decreased along with the onset of pre-eclampsia Conclusions: Pregnancies can succeed in couples who are both kidney transplant recipients. However, there might be higher risks of infertility, prematurity, and low birth weight. [ABSTRACT FROM AUTHOR]

Objective: Comparison of two different intervals of misoprostol administration after mifepristone in second trimester abortions. Materials and methods: This 12-month prospective study was conducted at a tertiary care facility. Only pregnancies with congenital deformity or sterilisation failure were included in the study's recruitment of 100 women who visited the hospital for a second trimester abortion between 12 and 20 weeks; cases with scarred uteri were omitted. In a systematic random selection of 50 women in each group, the administration of 200 mg of mifepristone orally was followed by two distinct intervals of intravaginal misoprostol administration at 24- and 48-hour intervals. After 24 hours, group A women received intravaginal 400 mcg misoprostol three hourly, up to a maximum of five doses, while group B received the same doses after 48 hours. Induction abortion interval noted on various parameters and paired t test and chi square test applied. Results: The mean IAI following misoprostol administration was 8.14 2±.03 hours in group A and 7.71 ±2.56 hours in group B. This difference was statistically insignificant. Average misoprostol doses for group A were 1.68±0.71 and for the group, B were 1.68±0.84; both doses were found to be statistically insignificant when used to induce abortion. All women aborted successfully in each group. There was no significant difference in side effects in both groups. Conclusion: Based on the results it was observed that shorter interval between mifepristone and misoprostol i.e., 24 hours can be chosen to decrease the hospital stay as there was no significant difference was seen after intravaginal misoprostol in terms of induction abortion interval, number of doses and side effects. [ABSTRACT FROM AUTHOR]

Pregnancy after kidney transplantation (KT) conveys risks of adverse pregnancy outcomes (APO). Little is known about performance of pre-pregnancy counselling after KT. This study investigated perceptions of risk, attitudes towards pregnancy and factors influencing advice given at pre-pregnancy counselling after KT. A web-based vignette survey was conducted among nephrologists and gynaecologists between March 2020 and March 2021, consisting of five vignettes containing known risk factors for APO and general questions on pre-pregnancy counselling after KT. Per vignette, attitudes towards pregnancy and estimation of outcomes were examined. In total 52 nephrologists and 25 gynaecologists participated, 56% from university hospitals. One third had no experience with pregnancy after KT. All gave positive pregnancy advice in the vignette with ideal circumstances (V1), versus 83% in V2 (proteinuria), 81% in V3 (hypertension), 71% in V4 (eGFR 40 ml/min/1.73 m²). Only 2% was positive in V5 (worst-case scenario). Chance of preeclampsia was underestimated by 89% in V1. 63% and 98% overestimated risk for graft loss in V4 and V5. Professionals often incorrectly estimated risk of APO after KT. As experience with pregnancy after KT was limited among professionals, patients should be referred to specialised centres for multidisciplinary pre-pregnancy counselling to build experience and increase consistency in given advice. [ABSTRACT FROM AUTHOR]

INTRODUCTION The aim of this retrospective study was to investigate all obstetric anaesthesia procedures at Mater Dei Hospital (MDH) in 2019 to better understand the care provided by anaesthetists to parturients. METHODOLOGY Data was collected from the obstetric anaesthesia logbook, a paper record in which the duty anaesthetist at the Central Delivery Suite (CDS) lists all anaesthetic interventions carried out over the previous 24 hours. All procedures were entered into a spreadsheet and coded. Calculations were then carried out to work out five parameters: the Caesarean section rate, the epidural uptake rate, the regional anaesthesia rate, the anaesthetic intervention number, and the Obstetric Anaesthesia Activity Index (OAAI). RESULTS There were 4040 deliveries at MDH in 2019. 1194 lower segment Caesarean sections (LSCS) were recorded in the obstetric anaesthesia logbook and the Caesarean section rate was 29.6%. A total of 966 spinal anaesthetics were carried out, 907 (94%) of which were for a LSCS. 1064 epidural catheters were inserted for labour analgesia, with a 26.3% epidural uptake rate for 2019. There were 109 parturients who required a general anaesthetic. The anaesthetic intervention number was 2350 and the Obstetric Anaesthesia Activity Index was 7.09. CONCLUSION The parameters listed above are described and compared to international guidelines and other descriptive studies. With 2350 anaesthetic interventions in obstetrics, anaesthetists were actively involved in the care of over half of all parturients at MDH in 2019 and this confirms the wide and considerable role anaesthetics has in maternal services provided at MDH. [ABSTRACT FROM AUTHOR]

Objective: To distinguish between prostaglandin and prostamide concentrations in the amniotic fluid of women who had an episode of preterm labor with intact membranes through the utilisation of liquid chromatography-tandem mass spectrometry.Study Design: Liquid chromatography-tandem mass spectrometry analysis of amniotic fluid of women with preterm labor and (1) subsequent delivery at term (2) preterm delivery without intra-amniotic inflammation; (3) preterm delivery with sterile intra-amniotic inflammation (interleukin (IL)-6>2.6 ng/mL without detectable microorganisms); and (4) preterm delivery with intra-amniotic infection [IL-6>2.6 ng/mL with detectable microorganisms].Results: (1) amniotic fluid concentrations of PGE2, PGF2α, and PGFM were higher in patients with intra-amniotic infection than in those without intra-amniotic inflammation; (2) PGE2 and PGF2α concentrations were also greater in patients with intra-amniotic infection than in those with sterile intra-amniotic inflammation; (3) patients with sterile intra-amniotic inflammation had higher amniotic fluid concentrations of PGE2 and PGFM than those without intra-amniotic inflammation who delivered at term; (4) PGFM concentrations were also greater in women with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation who delivered preterm; (5) amniotic fluid concentrations of prostamides (PGE2-EA and PGF2α-EA) were not different among patients with preterm labor; (6) amniotic fluid concentrations of prostaglandins, but no prostamides, were higher in cases with intra-amniotic inflammation; and (7) the PGE2:PGE2-EA and PGF2α:PGF2α-EA ratios were higher in patients with intra-amniotic infection compared to those without inflammation.Conclusions: Mass spectrometric analysis of amniotic fluid indicated that amniotic fluid concentrations of prostaglandins, but no prostamides, were higher in women with preterm labor and intra-amniotic infection than in other patients with an episode of preterm labor. Yet, women with intra-amniotic infection had greater amniotic fluid concentrations of PGE2 and PGF2α than those with sterile intra-amniotic inflammation, suggesting that these two clinical conditions may be differentiated by using mass spectrometric analysis of amniotic fluid. [ABSTRACT FROM AUTHOR]

Cervical epithelial cells play a central role in cervical remodeling (CR) during pregnancy and cervical events during menstrual cycle, including mounting physical and immunological barriers, proliferation and differentiation, maintenance of fluid balance, and likely in withstanding the mechanical force exerted by the growing fetus prior to term. In the present study, we attempt to decipher the specific roles of VEGF in fetal human cervical epithelial cells by delineating VEGF signature genes using RNA sequencing in order to characterize the specific biological effects of VEGF in these cells. Out of a total of 25,000 genes screened, 162 genes were found to be differentially expressed in human cervical epithelial cells, of which 12 genes were found to be statistically significantly differentially expressed. The differentially expressed genes (162) were categorized by biological function, which included (1) proliferation, (2) immune response, (3) structure/matrix, (4) mitochondrial function, and (5) cell adhesion/communication and others (pseudogenes, non-coding RNA, miscellaneous genes, and uncharacterized genes). We conclude that VEGF plays a key role in CR by altering the expression of genes that regulate proliferation, immune response, energy metabolism and cell structure, and biological processes that are essential to development and likely CR. [ABSTRACT FROM AUTHOR]

Introduction: The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABAA receptor. Whether neurosteroid levels and the function of the GABAA receptor are involved in the risk of preterm labour in pregnant women is unknown. Methods: Pregnant women with (n = 16) or without (n = 20) threatened preterm labour (TPL) in gestational week 33 + 6 days to 37 + 0 days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABAA receptor function in both groups was measured with a saccadic eye velocity test (SEVT). Results: Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0 pmol/L, respectively, p =.021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels in the TPL group (B: −3.2, 95% confidence interval (CI): −5.5 to −0.9, p =.012). As a predictor of TPL, progesterone was associated with cervix maturity (odds ratio: 1.02, 95% CI: 1.00–1.04, p =.038). SEVT showed that the women in both groups had similar GABAA receptor functions. In both groups, body mass index correlated with peak saccadic eye velocity (r =.34, p =.044) and negatively with allopregnanolone (r = −.41, p =.013). Conclusions: Neurosteroid levels were unchanged in the peripheral blood of women with TPL, despite the increase in available oxytocin. Although the function of the GABAA receptor was unchanged in women with TPL, to ensure reliable results, saccadic eye velocity should be investigated during a challenge test with a GABAA receptor agonist. [ABSTRACT FROM AUTHOR]

Background: Quantitative proteomics is an invaluable tool in biomedicine for the massive comparative analysis of protein component of complex biological samples. In the last two decades, this technique has been used to describe proteins potentially involved in the pathophysiological mechanisms of preeclampsia as well as to identify protein biomarkers that could be used with diagnostic/prognostic purposes in pre-eclampsia. Results: We have done a systematic review of all proteomics-based papers describing differentially expressed proteins in this disease. Searching Pubmed with the terms pre-eclampsia and proteomics, restricted to the Title/Abstract and to MeSH fields, and following manual curation of the original list, retrieved 69 original articles corresponding to the 2004–2020 period. We have only considered those results based on quantitative, unbiased proteomics studies conducted in a controlled manner on a cohort of control and pre-eclamptic individuals. The sources of biological material used were serum/plasma (n = 32), placenta (n = 23), urine (n = 9), cerebrospinal fluid (n = 2), amniotic fluid (n = 2) and decidual tissue (n = 1). Overall results were filtered based on two complementary criteria. First, we have only accounted all those proteins described in at least two (urine), three (placenta) and four (serum/plasma) independent studies. Secondly, we considered the consistency of the quantitative data, that is, inter-study agreement in the protein abundance control/pre-eclamptic ratio. The total number of differential proteins in serum/plasma (n = 559), placenta (n = 912), urine (n = 132) and other sources of biological material (n = 26), reached 1631 proteins. Data were highly complementary among studies, resulting from differences on biological sources, sampling strategies, patient stratification, quantitative proteomic analysis methods and statistical data analysis. Therefore, stringent filtering was applied to end up with a cluster of 18, 29 and 16 proteins consistently regulated in pre-eclampsia in placenta, serum/plasma and urine, respectively. The systematic collection, standardization and evaluation of the results, using diverse filtering criteria, provided a panel of 63 proteins whose levels are consistently modified in the context of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Despite the fact that case reports of intrauterine herpes simplex virus (HSV) infection have been published, this infection is not included herein, as the majority of neonatal HSV infections are acquired at birth as a consequence of direct fetal contact with the infected birth canal or through an ascending infection after premature rupture of the amniotic membranes. CMV infection may be acquired for the first time during pregnancy (primary infection) or it may result from reactivation of prior infection or reinfection with a different strain of the virus (non-primary infection). Nevertheless, a retrospective study of women with maternal primary infection in the index pregnancy found that, once the diagnosis of fetal infection had been made by PCR confirmation of CMV in the amniotic fluid, ultrasound was found to be more sensitive for the detection of subtle abnormalities associated with the fetal infection[18]. In common with other viral infections, however, the risk of an infected fetus being affected (i.e. risk of developing congenital defects) is greatest when infection occurs earlier in gestation: it is 97% when infection is before 12 weeks and 20% when it is from 12 to 16 weeks, while infection from 16 to 20 weeks is associated with a minimal risk of deafness only[[123], [142], [144]]. Diagnosis of fetal rubella infection Recommendations When primary infection occurs before 12 weeks' gestation, given the risk of fetal infection and the risk of an infected fetus developing severe abnormalities, termination of pregnancy can be considered, even without invasive testing ( B GOOD PRACTICE POINT b ). [Extracted from the article]

Background: Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms. Methods: Serum levels of placenta-related proteins–leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)–were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice. Results: An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs. Conclusions: Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model. [ABSTRACT FROM AUTHOR]

The cervix is the essential gatekeeper for birth. Incomplete cervix remodeling contributes to problems with delivery at or post-term while preterm birth is a major factor in perinatal morbidity and mortality in newborns. Lack of cervix biopsies from women during the period preceding term or preterm birth have led to use of rodent models to advanced understanding of the mechanism for prepartum cervix remodeling. The critical transition from a soft cervix to a compliant prepartum lower uterine segment has only recently been recognized to occur in various mammalian species when progesterone in circulation is at or near the peak of pregnancy in preparation for birth. In rodents, characterization of ripening resembles an inflammatory process with a temporal coincidence of decreased density of cell nuclei, decline in cross-linked extracellular collagen, and increased presence of macrophages in the cervix. Although a role for inflammation in parturition and cervix remodeling is not a new concept, a comprehensive examination of literature in this review reveals that many conclusions are drawn from comparisons before and after ripening has occurred, not during the process. The present review focuses on essential phenotypes and functions of resident myeloid and possibly other immune cells to bridge the gap with evidence that specific biomarkers may assess the progress of ripening both at term and with preterm birth. Moreover, use of endpoints to determine the effectiveness of various therapeutic approaches to forestall remodeling and reduce risks for preterm birth, or facilitate ripening to promote parturition will improve the postpartum well-being of mothers and newborns. [ABSTRACT FROM AUTHOR]

The steroid hormones progesterone (P4) and estradiol-17β (E2), produced by the placenta in humans and the ovaries in rodents, serve crucial roles in the maintenance of pregnancy, and the initiation of parturition. Because of their critical importance for species survival, the mechanisms whereby P4 and its nuclear receptor (PR) maintain myometrial quiescence during pregnancy, and for the decline in P4/PR and increase in E2/estrogen receptor (ER) function leading to parturition, are multifaceted, cooperative, and redundant. These actions of P4/PR include: (1) PR interaction with proinflammatory transcription factors, nuclear factor κB (NF-κB), and activating protein 1 (AP-1) bound to promoters of proinflammatory and contractile/contraction-associated protein (CAP) genes and recruitment of corepressors to inhibit NF-κB and AP-1 activation of gene expression; (2) upregulation of inhibitors of proinflammatory transcription factor activation (IκBα, MKP-1); (3) induction of transcriptional repressors of CAP genes (e.g., ZEB1). In rodents and most other mammals, circulating maternal P4 levels remain elevated throughout most of pregnancy and decline precipitously near term. By contrast, in humans, circulating P4 levels and myometrial PR levels remain elevated throughout pregnancy and into labor. However, even in rodents, wherein P4 levels decline near term, P4 levels remain higher than the Kd for PR binding. Thus, parturition is initiated in all species by a series of molecular events that antagonize the P4/PR maintenance of uterine quiescence. These events include: direct interaction of inflammatory transcription factors (e.g., NF-κB, AP-1) with PR; increased expression of P4 metabolizing enzymes; increased expression of truncated/inhibitory PR isoforms; altered expression of PR coactivators and corepressors. This article will review various mechanisms whereby P4 acting through PR isoforms maintains myometrial quiescence during pregnancy as well as those that underlie the decline in PR function leading to labor. The roles of P4- and E2-regulated miRNAs in the regulation and integration of these mechanisms will also be considered. [ABSTRACT FROM AUTHOR]

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Preeclampsia (PE) is one of the most significant pregnancy‐related hypertensive disorders. Currently, there are no useful markers to predict the onset of the condition in pregnant women. To provide further insights into the pathogenesis of PE and identify biomarkers of the condition, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomics coupled with 2‐D LC‐MS/MS, to analyze urinary protein profiles from 7 PE patients and 7 normotensive pregnant women. A total of 294 proteins were abnormally expressed in PE patients. Of these, 233 were significantly down‐regulated and 61 proteins were significantly up‐regulated. Bioinformatics analysis using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, found that the most differentially expressed proteins (DEPs) were involved in coagulation and complement pathways, the renin‐angiotensin system and cell adhesion molecules (CAMs) pathways. We further validated three of the DEPs, including serotransferrin (TF) and complement factor B (CFB) by immunoblottingand serum paraoxonase/arylesterase 1 (PON1) by ELISA using 14 pairs of urine samples from PE patients and normal pregnant women. Taken together, our results provide the basis for further understanding the pathogenesis of PE and identifying predictive biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage. Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words 'hypertension' and 'proteomics', and focused specifically on the most recent literature on the utility of proteomics in hypertension research. Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers. [ABSTRACT FROM AUTHOR]

Differential proteomic technology was used to identify urine proteomic profile of gestational hypertension and preeclampsia. Urine samples were collected from 10 patients with gestational hypertension, 10 patients with mild preeclampsia, 10 patients with severe preeclampsia and 10 normal pregnancies and analyzed by 2-D difference gel electrophoresis, then matrix assisted laser desorption ionization mass spectrometry was used to identify differential proteins. Subsequently, ELISA was used to verify the content variation of the identified proteins in 200 urine samples. In total, 30 differential proteins were identified. For prostaglandin-H2 D-isomerase (L-PGDS), perlecan and other 15 proteins, the contents in patients with gestational hypertension were higher than that of normal pregnancies, but lower in mild and severe preeclampsia. By contrast, serum albumin and α-1-antitrypsin was lower in samples from patients with gestational hypertension and higher in patients with mild and severe preeclampsia compared with normal pregnancies. ELISA verified that the urinary concentration of L-PGDS and perlecan were significantly lower in patients with preeclampsia than in normal pregnancies (P<0.05). Urine proteomics is a useful tool to identify potential biomarkers to distinguish between different types of hypertensive disorders in pregnancy. L-PGDS and perlecan could potentially be used as markers to reflect the state of renal function, and may participate in the genesis and development of renal injury during preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Reproductive function in women with end stage renal disease generally improves after kidney transplant. However, pregnancy remains challenging due to the risk of adverse clinical outcomes.Methods: We searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from date of inception through August 2017 for studies reporting pregnancy with kidney transplant.Results: Of 1343 unique studies, 87 met inclusion criteria, representing 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 ± 2.4 years. The live-birth rate was 72.9% (95% CI, 70.0-75.6). The rate of other pregnancy outcomes was as follows: induced abortions (12.4%; 95% CI, 10.4-14.7), miscarriages (15.4%; 95% CI, 13.8-17.2), stillbirths (5.1%; 95% CI, 4.0-6.5), ectopic pregnancies (2.4%; 95% CI, 1.5-3.7), preeclampsia (21.5%; 95% CI, 18.5-24.9), gestational diabetes (5.7%; 95% CI, 3.7-8.9), pregnancy induced hypertension (24.1%; 95% CI, 18.1-31.5), cesarean section (62.6, 95% CI 57.6-67.3), and preterm delivery was 43.1% (95% CI, 38.7-47.6). Mean gestational age was 34.9 weeks, and mean birth weight was 2470 g. The 2-3-year interval following kidney transplant had higher neonatal mortality, and lower rates of live births as compared to > 3 year, and < 2-year interval. The rate of spontaneous abortion was higher in women with mean maternal age < 25 years and > 35 years as compared to women aged 25-34 years.Conclusion: Although the outcome of live births is favorable, the risks of maternal and fetal complications are high in kidney transplant recipients and should be considered in patient counseling and clinical decision making. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual's blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases. Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches. Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Progesterone helps maintain cervical structure during pregnancy via the progesterone receptor (PR). Two PR isoforms exist, PR-A and PR-B, which have overlapping as well as isoform-specific target genes. During late gestation, leukocytes infiltrate the cervical stroma accompanied by increased cervical cytokine levels, resembling an inflammatory process. We examined interleukin (IL)-1β regulation of the expression of PR-A, PR-B, and genes governing prostaglandin synthesis in human cervical fibroblasts (HCFs). Since progesterone has been shown to exert anti-inflammatory actions, we also examined the capacity of progesterone (R5020) to ameliorate the actions of IL-1β in HCFs. Interleukin-1β induced both PR-A and PR-B mRNA in HCFs. Interleukin-1β induced a rapid and transient loss of both PR-A and PR-B protein, followed by a latent (24 hours) increase in both PR isoforms. R5020 negated the IL-1β-induced increase in PR-A and PR-B mRNA and protein as well as the rapid IL-1β-induced downregulation of nuclear PR. Interleukin-1β induced prostaglandin G/H synthase-2 (PGHS-2), but not prostaglandin G/H synthase-1 (PGHS-1), as well as prostaglandin E synthase-1 (PGES-1), but not prostaglandin F synthase (PGFS). R5020 did not ameliorate IL-1β induction of PGHS-2 or PGES-1. Blockade of prostaglandin synthesis (indomethacin) prevented both the IL-1β-induced increase in PR mRNA and the acute decrease in PR-A and PR-B protein, implicating a role for prostaglandins in regulating PR expression in HCFs. Although progesterone may function to maintain PR expression in a milieu of increasing cytokines in the late gestation human cervix, it does not exert an anti-inflammatory role with regard to prostaglandin E2 (PGE2) production. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.Objective: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins.Methods: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex ProTM Human Cancer Biomarker Panels 1 and 2.Results: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8-29.8 times in the study population.Conclusion: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered. [ABSTRACT FROM AUTHOR]

Background: Decidual cells play a role in the modulation of the innate immune response to protect pregnancy against infection. Steroid hormones regulate the innate immune response in different tissues, and they are involved in several biological processes like decidualization. The aim of this study was to assess if steroid hormones modulate the innate immunity in endometrial stromal cells (ESCs) and decidual stromal cells (DSCs) in response to group B streptococcus (GBS) infection in vitro.Methods: Primary cultures of ESC were differentiated into DSC using 36 nM estradiol + 300 nM progesterone, and both were infected with GBS overnight. Concentrations of pro- and anti-inflammatory mediators (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, IL-10, and TGF-β), chemokines (IL-8 and GCP-2), and human β-defensins (HBD-1, HBD-2, and HBD-3) were measured in the culture supernatants.Results: DSCs showed a significant increase in IL-6 (p < 0.05), TNF-α (p < 0.05), IL-10 (p < 0.01), and TGF-β (p < 0.05) secretion after GBS infection, while these changes were not observed in infected ESCs. IL-8 and GCP-2 increased after GBS infection, regardless of decidualization. β-Defensins 1-3 decreased (p < 0.05) in ESCs after GBS infection, and hormone decidualization preserved the secretion of these antimicrobial peptides.Conclusions: Decidualization mediated by steroid hormones balance the pro- and anti-inflammatory response at the maternal-fetal interface under infection conditions. [ABSTRACT FROM AUTHOR]

Problem The effectiveness of progesterone (P4) treatment for preventing preterm births is unclear. Its effects on the uterine cervix were tested using cultured human uterine cervical fibroblasts ( UCFs). Method of study UCFs were incubated with lipopolysaccharide ( LPS) in the presence or absence of P4 under various conditions. mRNA was subjected to PCR arrays and real-time RT- PCR to assess IL-6, IL-8, IL-1beta, PTGS2, MMP-1, and CXCL10 expression. Results When exposed to a high- LPS concentration (2.0 μg/ mL), expression of these genes was not suppressed by simultaneous P4 (1.0 μmol/L) treatment, but it was significantly inhibited when P4 was administered 1 hour prior to LPS, with the exception of the chemokines IL-8 and CXCL10. Expression of all genes was restricted by P4 under low-level LPS (0.2 μg/ mL) stimulation, especially when administered prior to LPS treatment. Conclusion These data suggest that early or prophylactic P4 administration is an effective and important measure for reducing preterm birth risk. [ABSTRACT FROM AUTHOR]

Problem To characterize the amniotic fluid ( AF) inflammatory-related protein ( IRP) network in patients with a sonographic short cervix ( SCx) and to determine its relation to early preterm delivery ( ePTD). Method of study A retrospective cohort study included women with a SCx (≤25 mm; n=223) who had amniocentesis and were classified according to gestational age ( GA) at diagnosis and delivery ( ePTD <32 weeks of gestation). Results (i) In women with a SCx ≤ 22 1/7 weeks, the concentration of most IRPs increased as the cervix shortened; those with ePTD had a higher rate of increase in MIP-1α, MCP-1, and IL-6 concentrations than those delivering later; and (ii) the concentration of most IRPs and the correlation between several IRP pairs were higher in the ePTD group than for those delivering later. Conclusion Women with a SCx at 16-22 1/7 weeks have a unique AF cytokine network that correlates with cervical length at diagnosis and GA at delivery. This network may aid in predicting ePTD. [ABSTRACT FROM AUTHOR]

Objective: To compare oral mifepristone (400 mg) with trans-cervical balloon catheter for induction of labor (IOL) in post date women with previous one cesarean section (CS).Methods: In this randomized trial, post date pregnant women (gestation 40 weeks 5 days), with previous one low segment CS (no previous vaginal delivery) were induced either with oral mifepristone (400 mg) or balloon catheter [Foley's catheter (16 Fr); bulb filled with 30 ml normal saline]. They were re-assessed 24 and 48 h later. If at any time Bishop Score was >6; amniotomy was done, followed by oxytocin infusion. Primary outcome of the study was labor onset after first manoeuvre. Secondary outcomes were cervical ripening, need of oxytocin, vaginal delivery and CS, in two groups.Results: From June 2012 to September 2015, we enrolled 107 women. Out of these, 57 received oral tablet mifepristone (400 mg) and 50 were inserted with balloon catheter. Labor onset after first manoeuvre was statistically significantly more in mifepristone group (37/57 vs. 13/50, respectively; p value 0.000). Bishop Score after 24 h was better in balloon catheter (p value 0.000). More women with balloon catheter required oxytocin for IOL (37/50 vs. 20/57, respectively; p value 0.000) along with higher dose [840 (320) mU vs 560 (120) mU, respectively, p value 0.000]. Failure of induction was statistically significantly higher in balloon catheter group (8 out of 50 vs. 2 out of 57, respectively, p value 0.043). There was no statistically significant difference in normal delivery or CS in either group (p value 0.242 and 0.331, respectively).Conclusion: Oral mifepristone (400 mg) is associated with statistically significantly higher incidence of labor onset in post date pregnant women with previous one CS, as compared to balloon catheter. Both methods are primarily for cervical ripening and oxytocin should not be delayed in the absence of onset of labor.Clinical Trial Registration: Clinical Trials Registry-India, www.ctri.nic.in , CTRI/2012/05/003634. [ABSTRACT FROM AUTHOR]

Objective(s) and design: The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells) of women with mild preeclampsia. Materials and methods: We recruited 21 women between 25–40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group. To assess the concentration of 11 sphingolipids in the blood plasma and blood fractions, we used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS). Results: We showed a significant increase in the concentration of eight sphingolipids in the plasma of women with preeclampsia in comparison to the control group: Sph (p = 0.0032), S1P (p = 0.0289), C20-Cer (p < 0.0001), C18-Cer (p < 0.0001), C16-Cer (p = 0.012), C18:1-Cer (p = 0.003), C22-Cer (p = 0.0071), and C24:1-Cer (p = 0.0085). Conclusion: We showed that selected sphingolipids, especially C20-Cer and C18-Cer, are totally new factors in the pathomechanism of PE and that these bioactive lipids may play an important role in apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

Relaxin is a small heterodimeric peptide hormone of the insulin/relaxin superfamily produced mainly in female and male reproductive organs. It has potent antifibrotic, vasodilatory and angiogenic effects and regulates the normal function of various physiological systems. Preclinical studies and recent clinical trials have shown the promise of recombinant relaxin as a therapeutic agent in the treatment of cardiovascular and fibrotic diseases. However, there are the universal drawbacks of peptide-based pharmacology that apply to relaxin: a short half-life in vivo requires its continuous delivery, and there are high costs of production, storage and treatment, as well as the possibility of immune responses. All these issues can be resolved by the development of low non-peptide MW agonists of the relaxin receptors which are stable, bioavailable, easily synthesized and specific. In this review, we describe the discovery and characterization of the first series of such compounds. The lead compound, ML290, binds to an allosteric site of the relaxin GPCR, RXFP1. ML290 shows high activity and efficacy, measured by cAMP response, in cells expressing endogenous or transfected RXFP1. Relaxin-like effects of ML290 were shown in various functional cellular assays in vitro. ML290 has excellent absorption, distribution, metabolism and excretion properties and in vivo stability. The identified series of low MW agonists does not activate rodent RXFP1 receptors and thus, the production of a RXFP1 humanized mouse model is needed for preclinical studies. The future analysis and clinical perspectives of relaxin receptor agonists are discussed.Linked Articles: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc. [ABSTRACT FROM AUTHOR]

Preeclampsia is a multisystem disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify dysregulated genes in maternal whole blood samples which may be associated with the development of preeclampsia. Whole blood samples were obtained at 28 wk of gestation from 5 women who later developed preeclampsia (cases) and 10 matched women with normotensive pregnancies (controls). Placenta samples were obtained from an independent cohort of 19 women with preeclampsia matched with 19 women with normotensive pregnancies. We studied gene expression profiles using Illumina microarray in blood and validated changes in gene expression in whole blood and placenta tissue by qPCR. We found a transcriptional profile differentiating cases from controls; 336 genes were significantly dysregulated in blood from women who developed preeclampsia. Functional annotation of microarray results indicated that most of the genes found to be dysregulated were involved in inflammatory pathways. While general trends were preserved, only HLA-A was validated in whole blood samples from cases using qPCR (2.30- ± 0.9-fold change) whereas in placental tissue HLA-DRB1 expression was found to be significantly increased in samples from women with preeclampsia (5.88- ± 2.24-fold change). We have identified that HLA-A is upregulated in the circulation of women who went on to develop preeclampsia. In placenta of women with preeclampsia we identified that HLA-DRB1 is upregulated. Our data provide further evidence for involvement of the HLA gene family in the pathogenesis of preeclampsia. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to assess the effect of vaginal progesterone as an adjuvant therapy to physical-exam-indicated cervical cerclage (PEICC). Methods This retrospective cohort study included 53 consecutive singleton women who underwent PEICC because of acute cervical insufficiency at 17-24 gestational weeks. The study population was divided into two groups: the adjuvant progesterone group ( n = 18) and the non-adjuvant group ( n = 35). A 200-mg dose of vaginal micronized natural progesterone was administered after cerclage in the adjuvant progesterone group. Primary outcome measure was spontaneous preterm birth (SPTB) at <36 weeks. Results The SPTB rate at <36 weeks in the adjuvant group was significantly lower than in the non-adjuvant group (17% vs 51%, P < 0.05). Adjuvant progesterone therapy was significantly associated with a reduction in SPTB at <36 weeks (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.69, P < 0.05) even after adjusting for known covariates, including a visible membrane size of ≥4 cm, gestational age, prior SPTB, and use of amnioreduction. The frequency of SPTB at <32 weeks, birthweight < 2500 g, and neonatal intensive care unit admission was significantly lower in the adjuvant progesterone group than in the non-adjuvant group ( P < 0.05 for all). Conclusion Adjuvant vaginal progesterone therapy with PEICC was associated with reductions in SPTB, low birthweight, and neonatal intensive care unit admission. [ABSTRACT FROM AUTHOR]

Hypertensive disorders in pregnancy have been the cause of much clinical dilemma, affecting up to 10 % of all pregnancies. The precise blood pressure to achieve in a pregnant woman is usually a battle between minimizing end organ damage to the mother and providing adequate perfusion to the placenta and the fetus. This predicament is becoming more, not less, frequent as maternal ages increase in high resource nations. Biomarkers to predict preeclampsia, a subcategory of hypertension in pregnancy, have always been elusive. The discovery of angiogenic factors relevant to preeclampsia in the last decade, however, has propelled much needed research, both in the basic science and clinical arenas. In this review, we summarize the latest clinical studies and international guidelines on blood pressure goals in pregnancy, and discuss the most promising of biomarkers to predict or diagnose preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of 'mifepristone' for induction of labor (IOL) in pregnant women with prior cesarean section (CS). Methods: In this retrospective study, all pregnant women with prior CS who received oral mifepristone (400 mg) for IOL (as per clear obstetric indications) [group 1] were compared with pregnant women with prior CS who had spontaneous onset of labor (SOL) [group 2], with respect to incidence of vaginal delivery, CS, duration of labor, and various maternal and fetal outcomes. Results: During the study period, 72 women received mifepristone (group 1) for IOL and 346 had SOL (group 2). In group 1 after mifepristone administration, 40 (55.6 %) women had labor onset, and 24 (33.3 %) women had cervical ripening (Bishop Score ≥ 8) within 48 h. There were no statistically significant differences with respect to duration of labor ( p value: 0.681), mode of delivery (i.e., normal delivery or CS- p value: 0.076 or 0.120, respectively), or maternal (blood loss or scar dehiscence/rupture uterus), or fetal outcomes (NICU admission) compared to women with previous CS with SOL (group 2). However, the need of oxytocin ( p value 0.020) and dose of oxytocin requirement ( p value 0.008) were more statistically significant in group 1. Conclusion: Mifepristone may be considered as an agent for IOL in women with prior CS. [ABSTRACT FROM AUTHOR]

Background: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.Methods: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4. In Part A of the study, safety evaluation of three escalating doses of serelaxin (7.5, 25 or 75 μg/kg/day) or placebo was performed in 22 subjects admitted to the hospital 24 h prior to scheduled induction (n = 7, 4, 4, and 7 subjects, respectively). The highest safe dose from Part A and placebo were then tested in Part B for safety and cervical ripening (n = 25 subjects/arm). Planned randomisation ratio was of 4:2 (serelaxin:placebo) for each dose group in Part A and 1:1 for Part B. For analysis, subjects in Part B were pooled with those receiving the same dose in Part A and all subjects receiving placebo were pooled. The primary efficacy endpoint was change from baseline in Bishop score at 6, 12 and 24 h or end of study drug administration. Maternal safety evaluations included adverse events and vital signs through 4 weeks. Fetal assessments included serial heart rate monitoring and nonstress testing. Neonatal assessments included Apgar scores, NICU admissions, and adverse events through 4 weeks.Results: Overall, 74 subjects were randomized and 72 were treated. There were no significant differences between the groups receiving the highest safe dose of serelaxin (75 μg/kg/day) and placebo in the primary or secondary efficacy endpoints. Changes from baseline in Bishop score at 24 h were 4.19 ± 1.9 and 3.26 ± 2.26 in the pooled placebo and serelaxin groups, respectively (p = 0.2507). Serelaxin was well tolerated and no anti-serelaxin antibodies were detected in either subjects or neonates.Conclusion: Serelaxin infusion at the end of pregnancy was well tolerated but did not advance cervical ripening.Trial Registration: Clinicaltrials.gov identifier NCT00259103 (15 November 2005). [ABSTRACT FROM AUTHOR]

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments.In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with fetal shunt dislodgement in lower urinary tract obstruction (LUTO).Methods: We conducted a retrospective study of 42 consecutive fetuses with a diagnosis of LUTO in a tertiary fetal center between April 2013 and November 2015. Possible factors associated with prenatal shunt dislodgment were evaluated in fetuses who underwent shunt placement, including gestational age at diagnosis, gestational age at procedure, presence of 'keyhole sign', initial fetal bladder volume and wall thickness, prenatal ultrasonographic renal characteristics, amniotic fluid volume, presence of ascites prior to shunting, and type of fetal shunt.Results: Nineteen (46.3%) fetuses underwent shunt placement at a median gestational age of 19 (range: 16.3-31.1) weeks. Shunt dislodgement occurred in 10 (52.6%) patients. A total of 35 procedures were performed; among which 16 (45.7%) were repeat procedures. The only prenatal factor associated with shunt dislodgement was the type of the shunt; Kaplan-Meier analysis indicated that the Rocket was associated with increased likelihood of remaining orthotopic (p = 0.04).Conclusion: Fetal shunt dislodgement occurs in approximately half of the patients and appears to be associated with the type of the shunt. Future research is necessary to develop better shunt systems and to investigate different fetal therapeutic approaches. © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The current definition of hypertension is based on blood pressure values, and blood pressure also drives treatment decisions, is the most important treatment monitoring tool and helps estimating risk of hypertension-related organ damage. In an era of precision medicine, additional biomarkers are needed in the diagnosis and management of patients with hypertension. In this review, we outline the areas in which functional, imaging and circulating biomarkers could help in a more individualised definition of hypertension and associated risk. We will cover biomarkers for diagnosis; of patho-physiology and prediction of hypertension; response to treatment, organ damage; and to monitor treatment. A clear focus is on the vasculature, the heart and the kidneys, whereas we see a need to further develop biomarkers of cerebral function in order to diagnose cognition deficits and monitor changes in cognition in the future to support addressing the growing burden of hypertension-associated vascular dementia. [ABSTRACT FROM AUTHOR]

Objective: Prostaglandins (PGs) are considered the universal mediators of parturition. Amniotic fluid PGE2and PGF2αconcentrations increase before the onset of spontaneous labor at term, as well as during labor. This study was conducted to determine if the concentrations of umbilical cord PGE2and PGF2α change with advancing gestational age, spontaneous labor at term, and preterm labor (with and without funisitis). Methods: Umbilical cord (UC) tissue samples were obtained from women (N = 158) with singleton pregnancies in the following groups: (1) term deliveries without labor (TNL;n = 20); (2) term deliveries with labor (TIL;n = 20); (3) spontaneous preterm deliveries (sPTD) with (n = 20) and without acute funisitis (n = 20); and (4) preeclampsia without labor (n = 78). The concentrations of PGs were determined in different locations of the UC. PGE2and PGF2αwere measured by specific immunoassays. Non-parametric statistics were used for analysis. Results: (1) In spontaneous preterm deliveries, the median UC PGE2concentration was higher in cases with funisitis than in those without funisitis (233.7 pg/µg versus 87.4 pg/µg of total protein,p = 0.001); (2) the median UC PGE2concentration in sPTD with funisitis was also higher than that obtained from samples who had undergone labor at term (233.7 pg/µg versus 116.1 pg/µg of total protein,p = 0.03); (3) the UC PGE2and PGF2αconcentration increased as a function of advancing gestational age before 36 weeks (PGE2: ρ = 0.59,p < 0.001; PGF2α: ρ = 0.39,p = 0.01), but not after 36 weeks (PGE2: ρ = −0.1,p = 0.5; PGF2α: ρ = −0.2,p = 0.2); (4) the median UC concentrations of PGE2and PGF2αat term was similar in samples obtained from women with and without labor (PGE2: TNL 133.7 pg/µg versus TIL 116.1 pg/µg of total protein,p = 0.9; PGF2α: TNL 8.4 pg/µg versus TIL 8.1 pg/µg of total protein,p = 0.7); and (5) there was no correlation between UC PG concentration and gestational age at term pregnancy (PGE2: ρ = 0.01,p = 0.9; PGF2α: ρ = 0.07,p = 0.7). Conclusions: (1) PGE2concentrations in the UC are higher in the presence of acute funisitis than in the absence of this lesion; (2) spontaneous labor at term was not associated with a change in the UC concentration of PGE2and PGF2α; and (3) the UC concentrations of PGE2and PGF2αincreased as a function of gestational age. We propose that UC PGs act as inflammatory mediators generated in the context of fetal systemic inflammation. [ABSTRACT FROM PUBLISHER]

Venous thromboembolism (VTE), which may manifest as pulmonary embolism (PE) or deep vein thrombosis (DVT), is a serious and potentially fatal condition. Treatment and prevention of obstetric-related VTE is complicated by the need to consider fetal, as well as maternal, wellbeing when making management decisions. Although absolute VTE rates in this population are low, obstetric-associated VTE is an important cause of maternal morbidity and mortality. This manuscript, initiated by the Anticoagulation Forum, provides practical clinical guidance on the prevention and treatment of obstetric-associated VTE based on existing guidelines and consensus expert opinion based on available literature where guidelines are lacking. [ABSTRACT FROM AUTHOR]

Progesterone (P4) maintains uterine quiescence during the majority of pregnancy, whereas diminished progesterone receptor (PR) expression and/or activity (ie, functional P4 withdrawal) promotes parturition. To investigate the regulation of PR expression in cervical stroma, fibroblasts from premenopausal hysterectomy specimens were prepared. Greater than 99% of the cultures were vimentin positive (mesenchymal cell marker) with only occasional cytokeratin-8 positivity (epithelial cell marker) and no evidence of CD31-positive (endothelial cell marker) cells. Cells were immunolabeled with antibodies directed against PRs (PR-A and PR-B), estrogen receptor α (ER-α), and glucocorticoid receptor-α/β (GR-α/β). All cells were uniformly immunopositive for ER-α and GR-α/β but did not express PRs. Incubation of cells with 10−8 mol/L 17β-estradiol induced a time-dependent increase in PR-A and PR-B messenger RNAs (mRNAs) by quantitative real-time polymerase chain reactions and proteins by immunoblotting and immunofluorescence. Incubation of cervical fibroblasts with PR ligands (medroxyprogesterone acetate or Org-2058) downregulated PR-A and PR-B levels. Coincubation of cells with PR ligands plus RU-486, a PR antagonist, partially abrogated agonist-induced receptor downregulation. Dexamethasone, a pure glucocorticoid, had no inhibitory effect on PR expression. These results indicate that progestins and estrogens regulate PR expression in cervical fibroblasts. We postulate that hormonal regulation of PR expression in the cervical stroma may contribute to functional P4 withdrawal in preparation for parturition. [ABSTRACT FROM AUTHOR]