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Preeclampsia is a major determinant of fetal and maternal morbidity and mortality. We used a proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset of disease. We prospectively collected urine samples from women throughout pregnancy. Samples from gestational weeks 12 to 16 (n=45), 20 (n=50), and 28 (n=18) from women who subsequently had preeclampsia develop were matched to controls (n=86, n=49, and n=17, respectively). We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Disease-specific peptide patterns were generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. From comparison with nonpregnant controls, we defined a panel of 284 pregnancy-specific proteomic biomarkers. Subsequently, we developed a model of 50 biomarkers from specimens obtained at week 28 that was associated with future preeclampsia (classification factor in cases, 1.032 ± 0.411 vs controls, -1.038 ± 0.432; P<0.001). Classification factor increased markedly from week 12 to 16 to 28 in women who subsequently had preeclampsia develop (n=16; from -0.392 ± 0.383 to 1.070 ± 0.383; P<0.001) and decreased slightly in controls (n=16; from -0.647 ± 0.437 to -1.024 ± 0.433; P=0.043). Among the biomarkers are fibrinogen alpha chain, collagen alpha chain, and uromodulin fragments. The markers appear to predict preeclampsia at gestational week 28 with good confidence but not reliably at earlier time points (weeks 12-16 and 20). After prospective validation in other cohorts, these markers may contribute to better prediction, monitoring, and accurate diagnosis of preeclampsia.

Inhibins are regulators of paracrine and endocrine function during pregnancy, but their intrauterine sites of secretion are not well established. In amniotic fluid, inhibin A-, inhibin B- and inhibin pro-alphaC-containing isoforms were present in high concentrations, whereas in maternal serum, inhibin A and pro-alphaC forms were present in high amounts, with low concentrations of inhibin B. In fetal cord serum, inhibin pro-alphaC was present in all samples, inhibin B was detectable in male but not female fetuses, with no detectable inhibin A in either sex. From cultured explants, both inhibin A and B were secreted by chorion laeve, whereas only inhibin A was secreted by placenta, with both tissues secreting inhibin pro-alphaC. Only low concentrations of both dimeric inhibins and pro-alphaC forms were secreted by decidua parietalis and amnion. The dual perfused placental cotyledon secreted both inhibin A and pro-alphaC into maternal perfusate, but only inhibin pro-alphaC into the fetal circulation and less than to the maternal side. We conclude that trophoblast is the predominant source of dimeric inhibins, but with markedly different secretion depending on its intrauterine location. There was a significant decrease in inhibin A and pro-alphaC in amniotic fluid collected at term active labour compared to elective Caesarean section (P < 0.001). This may reflect a local change in inhibin/activin processing at labour, likely in chorion laeve trophoblast cells, which may be important in the paracrine control of the feto-maternal communication required to maintain pregnancy and initiate labour.

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 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]

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]

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]

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]

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]

Proteome analysis is increasingly being used in investigations elucidating the molecular basis of disease, identifying diagnostic and prognostic markers, and ultimately improving patient care.We appraised the current status of proteomic investigations using human samples, including the state of the art in proteomic technologies, from sample preparation to data evaluation approaches, as well as key epidemiologic, statistical, and translational issues.We systematically reviewed the most highly cited clinical proteomic studies published between January 2009 and March 2014 that included a minimum of 100 samples, as well as strategies that have been successfully implemented to enhance the translational relevance of proteomic investigations. Limited comparability between studies and lack of specification of biomarker context of use are frequently observed. Nevertheless, there are initial examples of successful biomarker discovery in cross-sectional studies followed by validation in high-risk longitudinal cohorts. Translational potential is currently hindered, as limitations in proteomic investigations are not accounted for. Interdisciplinary communication between proteomics experts, basic researchers, epidemiologists, and clinicians, an orchestrated assimilation of required resources, and a more systematic translational outlook for accumulation of evidence may augment the public health impact of proteomic investigations. [ABSTRACT FROM AUTHOR]

The study of proteomics could explain many aspects of obstetric disorders. We undertook this review with the aim of assessing the utility of proteomics in the specialty of obstetrics. We searched the electronic databases of MEDLINE, EBSCOhost, BVS Bireme, and SciELO, using various search terms with the assistance of a librarian. We considered cohort studies, case-control studies, case series, and systematic review articles published until October 2014 in the English or Spanish language, and evaluated their quality and the internal validity of the evidence provided. Two reviewers extracted the data independently, then both researchers simultaneously revised the data later, to arrive at a consensus. The search retrieved 1,158 papers, of which 965 were excluded for being duplicates, not relevant, or unrelated studies. A further 86 papers were excluded for being guidelines, protocols, or case reports, along with another 64 that did not contain relevant information, leaving 43 studies for inclusion. Many of these studies showed the utility of proteomic techniques for prediction, pathophysiology, diagnosis, management, monitoring, and prognosis of pre-eclampsia, perinatal infection, premature rupture of membranes, preterm birth, intrauterine growth restriction, and ectopic pregnancy. Proteomic techniques have enormous clinical significance and constitute an invaluable weapon in the management of obstetric disorders that increase maternal and perinatal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (s Flt-1 also known as s VEGFR) and very low placenta growth factor ( PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine- γ-lyase (also known as CSE or Cth), which generate carbon monoxide ( CO) and hydrogen sulphide ( H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors s Flt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit [ABSTRACT FROM AUTHOR]

Objectives: To find out the clinical characteristics and risk factors for deep venous thrombosis (DVT) after gynecological surgery. Methods: Four hundred and ninety-eight patients treated surgically in the department of gynecology of our hospital from July 2012 to May 2014 were reviewed retrospectively. The data including patient age, gender, medical history, hospital stay, anesthesia type, operation time, occupation type, operative or postoperative medicine, perioperative bleeding, postoperative activity time, mortality rate and so on, were collected. Results: Among 498 patients, 58 were included in the thrombosis group, 423 patients in the non-thrombosis group and 17 patients were excluded. The incidence of deep venous thrombosis was 11.6%. In 58 cases with deep venous thrombosis, 6 cases developed pulmonary embolism and two patients died, the mortality rate for pulmonary embolism is 33.3%. In multivariate analysis, age, malignant tumor, cardiovascular comorbidity and postoperative hemostatics dose are independent risk factors, physical labour and minimally invasive surgery are protective factors for DVT. Conclusion: The patients with elder age, malignant tumor, cardiovascular comorbidity or large postoperative hemostatics dose should be paid high attention to and the minimally invasive surgery are optimal treatment in preventing DVT. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001). These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Preeclampsia is associated with a number of changes to maternal vascular function. Assessment of arterial stiffness using pulse wave analysis (PWA) has been proposed as a means of predicting preeclampsia before the onset of clinically detectable disease. One hundred and eighty women with 2 risk factors for preeclampsia were examined at gestational weeks 16 and 28, of whom 17 (9.4%) developed preeclampsia. To study the effects of pregnancy itself women were also examined at 6-9 months post-natally; an additional 30 healthy non-pregnant women were also examined. PWA was performed using SphygmoCor; augmentation index (AIx), a marker of arterial wave reflection, was also measured using EndoPAT-2000. Women who developed preeclampsia were more likely to be overweight and had a higher brachial and central diastolic BP at gestational week 16 than those who remained normotensive. There was no difference in any parameter of arterial wave reflection between non-pregnant and pregnant women, nor between those who developed preeclampsia and those who remained normotensive, when examined at weeks 16 and 28 or post-natally. In this cohort of women with risk factors for preeclampsia, PWA did not provide additional information beyond brachial blood pressure and maternal risk factor profile about the risk of future development of preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-’omics’ based discovery approach. Methods: Seven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment. Results: In addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively. Conclusions: Both early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods: We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results: Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = -0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions: Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a multisystem disorder of pregnancy, which complicates 3-5% of pregnancies. It is a major cause of maternal and neonatal mortality worldwide. Despite decades of research, the etiology of preeclampsia has remained unknown and undetectable prior to the onset of symptoms. The current review article discusses different aspects of preeclampsia in order to delineate the pathophysiology of the disease. Methods: This study has reviewed 96 publications explaining the various characteristics of preeclampsia including etiology, genetics, proteomics and metabolomics, using EBSCO, OVID, PubMed, Elsevier and NCBI databases. Findings: Based on the published studies, endothelial dysfunction and oxidative stress are the major problems in preeclampsia. Related genes and biomarkers are reported which may improve the diagnosis of preeclampsia. Proteomics and metabolomics have provided new insights into better understanding of the etiology and management of the disease. Conclusion: Preeclampsia is a complicated and multifactorial disease which needs to be evaluated in different aspects. This review article introduces novel approaches to the diagnosis and treatment of this disorder. [ABSTRACT FROM AUTHOR]

Proteomics, the study of the proteins making up the proteome, has emerged in recent years as an important tool in several different fields of medical research for early disease detection, for assessment of response to treatment and for unravelling underlying pathophysiological mechanisms. Although the majority of patients with hypertension are treated in a similar manner, the causes underlying the condition are diverse, and often poorly understood. Genetic studies have implicated several different candidate genes, but it may be that examination of the 'downstream' products of genes, the proteins, will help to improve understanding of the link between the environmental and genetic effects that contribute towards development of hypertension. Proteomic studies can be performed quickly and reliably on several different sample types including plasma and urine, requiring minimal pre-test preparation. In this review, we will compare the different analytical platforms and technical issues involved in proteomic analysis. We will discuss existing studies of proteomics in hypertension, as well as related conditions such as renal disease, pre-eclampsia and coronary artery disease. We will also explore potential future applications of proteomics-based research, which may ultimately lead to improved population screening, monitoring of therapy and early detection of target organ damage. [ABSTRACT FROM AUTHOR]

Proper cervical function is essential for a normal pregnancy and birth to occur. Understanding the mechanisms that take place in normal pregnancy will allow a better comprehension of the complications involved in premature cervical remodeling and lead to better methods of diagnostics and prevention for preterm birth. Unfortunately, human samples are not easily available, and samples that are collected are often confounded by variations in timing and region of cervix from which sample is collected. Animal models, specifically the mouse, have facilitated a great deal of exploration into the mechanisms of cervical function and pathways of preterm birth. This review highlights some of the groundbreaking discoveries that have arisen from murine research including 1) the identification of early pregnancy changes in collagen fibril processing and assembly that result in progressive modifications to collagen architecture with subsequent loss of tissue stiffness during pregnancy, 2) the determination that immune cells are not key to cervical ripening at term but have diverse phenotypes and functions in postpartum repair, and 3) the finding that the process of preterm cervical ripening can differ from term ripening and is dependent on the etiology of prematurity. These findings, which are relevant to human cervical biology, provide new insights that will allow targeted studies on the human cervix as well as identify potential biomarkers for early detection of premature cervical ripening and development of improved therapies to prevent premature ripening of the cervix and subsequent preterm birth. [ABSTRACT FROM AUTHOR]

Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the 'extravillous trophoblast' (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10-8 M), medroxyprogesterone acetate (10-7 M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on MatrigelTM were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLCMS/ MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro- DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that nondecidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states. [ABSTRACT FROM AUTHOR]

The mechanisms underlying detachment of foetal membranes after birth in cows are still unclear. To address this problem in a systematic manner, we performed the first holistic transcriptome study of bovine placentomes antepartum (AP; n=4 cows) and intrapartum (IP; n=4 cows) using Affymetrix GeneChip Bovine Genome Arrays. Three placentomes were extracted from each cow, and tissue samples from the contact zones of the placentomes (foeto-maternal units) were recovered by systematic random sampling and processed for RNA extraction and for stereological quantification of cellular composition. Statistical analysis of microarray data (false discovery rate 1%) revealed 759 mRNAs with at least twofold higher levels in the samples of the AP group, whereas 514 mRNAs showed higher levels in the IP group. The differentially expressed genes were classified according to biological processes and molecular functions using the Functional Annotation Clustering tool of the DAVID Bioinformatics Resources. Genes with higher mRNA levels in the AP group were nearly completely related to mitotic cell cycle and tissue differentiation. During parturition, a complete shift occurred because the genes with higher mRNA levels in IP were nearly all related to three different physiological processes/complexes: i) apoptosis, ii) degradation of extra cellular matrix and iii) innate immune response, which play a fundamental role in placental detachment. These results are an excellent basis for future studies investigating the molecular basis of retained foetal membranes. [ABSTRACT FROM AUTHOR]

Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% ( n = 21) vs 16.1% ( n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups. Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The author reflects on the importance of progesterone in the maintenance of pregnancy. He points out that a decline in levels of progesterone is believed to be central to the initiation of parturition in most mammalian species, including primates or humans. He mentions, however, that the administration of progestogen to prevent spontaneous miscarriage and preterm birth has been a subject of investigation for several decades.

The article presents a study on the preventive approach to obstetric care in a rural hospital in the U.S. It aims to compare cesarean delivery rates between physicians who used preventive induction and for those who did not. It used the prostaglandin-assisted preventive labor induction and a cohort design to compare birth outcomes. It was found that labor induction method had a lower cesarean delivery rate without increases in rates of adverse birth outcomes with warranted controlled trials.

Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives. [ABSTRACT FROM AUTHOR]

Objective To compare cervical clinical data, ultrasound parameters and fetal fibronectin assessment in the prediction of the duration of induced labor when the cervix is unfavorable. Methods This was a prospective study of 90 pregnant women with a Bishop score ≤5 undergoing labor induction. The Bishop score and its components, parity, cervical ultrasound parameters and fetal fibronectin level were analyzed using Cox's model in order to determine the most predictive factors for the duration of the latent and active phases of labor as well as its total duration. Results There was a significant correlation between duration of the latent phase and the whole of labor, and digitally assessed cervical dilatation (P = 0.003 and P < 0.001, respectively), parity (P = 0.006 and P < 0.001), the Bishop score (P = 0.019 and P = 0.003) and ultrasound-determined cervical length (P = 0.035 and P = 0.003). The length of the active phase of labor did not correlate with the cervical status. Funneling did not appear to be predictive of the duration of labor and it had a poor correlation with digital cervical dilatation. The length of the latent phase and that of the whole of labor was significantly longer when cervical dilatation was ≤2 cm (P < 0.001 in each case), when women were nulliparous (P = 0.002 and P < 0.001) and when ultrasound cervical length was ≥27 mm (P = 0.002 and P = 0.005). Conclusion Cervical dilatation as assessed by digital examination is the best predictor of the duration of the latent phase and of that of the whole of labor. Ultrasound measurement of cervical length is not more accurate at predicting the duration of labor than are clinical data. [ABSTRACT FROM AUTHOR]

Objective To compare the Bishop score, ultrasound cervical parameters and fetal fibronectin assessment for predicting failed labor induction when the cervix is unfavorable. Method A prospective observational study was performed in 106 consecutive pregnant women with a Bishop score ≤ 5 undergoing labor induction. Assessment of fetal fibronectin and ultrasound measurement of cervical length, cervical wedging and cervical lip areas were performed. The relationship between these parameters and failure of labor induction was determined. Results Failure of labor induction was defined as failure to reach a cervical dilatation of ≥ 5 cm, and it occurred in 16 patients (15.1%). Induction failure was associated with low Bishop scores before (P = 0.004) and 6 h after the start of induction (P = 0.00 7), increased clinical cervical length (P 0.02) and increased ultrasound anterior cervical lip area (P = 0.04). The logistic regression model identified the Bishop score before induction (odds ratio = 2.25; 95% Cl, 1.30-3.91; P = 0.003) and the clinical cervical length (odds ratio = 3.95; 95% Cl, 1.3 -11.7; P = 0.01) as being independent predictors of failed induction. To predict an induction failure, the best Bishop score cut-off value was 4, with a sensitivity of 8 7.5%, a specificity of 45.6%, a likelihood ratio of 1.58, a positive predictive value of 22.2% and a negative predictive value of 95.4%. Conclusion Compared with the Bishop score, cervical length by ultrasound is not a better predictor for the outcome of labor induction in an unfavorable cervix. Nevertheless, the Bishop score appears to be of poor predictive value for failed induction of labor. [ABSTRACT FROM AUTHOR]

Examines the localization of interleukin-6 and 8 in the lower uterine segment tissues during cervical dilatation. Association of cervical dilatation with increase inflammatory cytokines; Presence of interleukin-6 and 8 in glandular epithelium; Release of matrix metalloproteinases during granulocyte invasion.