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Introduction E-cigarette use during pregnancy is a risk factor for maternal and fetal health. Early studies on animals showed that in utero exposure to e-cigarettes can have negative health outcomes for the fetus. There has been only limited research into the risk perceptions of e-cigarette use during pregnancy. This study was conducted to comprehensively characterize the constructs of risk perceptions with regard to e-cigarette use during pregnancy using an I ntegrated H ealth B elief M odel (IHBM). Methods Our ST udy on E -cigarettes and P regnancy (STEP) used a mixed methods approach, with the study divided into an initial qualitative part and a quantitative part. A netnographic approach was used for the first part, which consisted of the analysis of 1552 posts from 25 German-language online discussion threads on e-cigarette use during pregnancy. Using these qualitative results, a quantitative questionnaire was developed to explore risk perception constructs about e-cigarette use during pregnancy. This questionnaire was subsequently administered to pregnant women (n = 575) in one hospital in Hamburg, Germany. Descriptive and bivariate analysis was used to examine differences in risk perception according to participants' tobacco and e-cigarette user status before and during pregnancy. While the study design, methods and sample have been extensively described in our recently published study protocol in the January 2020 issue of Geburtshilfe und Frauenheilkunde , this paper is devoted to a presentation of the results of our mixed methods study. Results Themes related to perceived threats identified in the qualitative study part were nicotine-related health risks and potential health risks of additional ingredients . Perceived benefits were possibility and facilitation of smoking cessation and a presumed potential to reduce harm . The subsequent quantitative part showed that nearly all participants (99.3%) perceived e-cigarettes which contained nicotine as constituting a threat to the health of the unborn child. The most commonly perceived barrier was health-related (96.6%), while the most commonly perceived benefit was a reduction in the amount of tobacco cigarettes consumed (31.8%). We found that particularly perceived benefits varied depending on the participant's tobacco and e-cigarette user status. Conclusion When considering future prevention strategies, the potential health risks and disputed effectiveness of e-cigarettes as a tool for smoking cessation need to be taken into account and critically discussed., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Intrahepatic cholestasis of pregnancy (ICP) is the most frequent pregnancy-specific liver disease. It is characterized by pruritus and an accompanying elevation of serum bile acid concentrations and/or alanine aminotransferase (ALT), which are the key parameters in the diagnosis. Despite good maternal prognosis, elevated bile acid concentration in maternal blood is an influencing factor to advers fetal outcome. The ICP is associated with increased rates of preterm birth, neonatal unit admission and stillbirth. This is the result of acute fetal asphyxia as opposed to a chronic uteroplacental insufficiency. Reliable monitoring or predictive tools (e.g. cardiotocography (CTG) or ultrasound) that help to prevent advers events are yet to be explored. Medicinal treatment with ursodeoxycholic acid (UDCA) does not demonstrably reduce adverse perinatal outcomes but does improve pruritus and liver function test results. Bile acid concentrations and gestational age should be used as indications to determine delivery. There is a high risk of recurrence in subsequent pregnancies., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2021.)

Around 3% of all pregnancies are complicated by preterm prelabor rupture of membranes (PPROM) before 37 + 0 weeks of gestation. Since PPROM is likely to be associated with microbial invasion of the amniotic cavity (MIAC)-either before or secondary to PPROM-the risk of developing intraamniotic inflammation (IAI) is high. IAI is associated with short latency to delivery and with adverse short- and long-term outcomes for the newborn, especially in cases of fetal inflammatory response syndrome (FIRS). Prediction of IAI based on maternal parameters is difficult or impossible. The recently established definition of triple I ("infection, inflammation, or both") is based on the parameter "maternal body temperature". If this is increased to ≥ 38.0 °C and there is no other reason to explain maternal fever, the finding is suspicious for triple I if at least one other of the following parameters can be found: fetal tachycardia > 160 bpm for at least 10 min, maternal leukocytes > 15,000/µl without administration of corticosteroids, or purulent fluid from the cervical os. Pregnancies suspicious for triple I should be terminated. The confirmation of triple I is only possible by placental histology (histologically confirmed chorioamnionitis, HCA). Confirmation based on amniocentesis (positive Gram stain, low glucose concentration [<14 mg/dl], elevated white blood cell count [>30 cells/mm 3 ], positive culture) takes too long and is unreliable. Serial determinations of C‑reactive protein also do not allow reliable diagnosis of IAI. Studies using interleukin 6 measurements from the posterior fornix and/or cervical os are promising methods, the validation of which is awaited., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2021.)

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Introduction During pregnancy, the mother's healthy lifestyle is crucial for the health of the fetus. Potential risk factors for maternal and child health should therefore be identified and reduced as early as possible. The consumption of e-cigarettes represents one of these potential risk factors. Exploring risk perceptions about e-cigarette use during pregnancy can provide early indications of possible user motives. Therefore, our mixed methods ST udy on E -cigarettes and P regnancy (STEP) aimed to comprehensively analyze risk perceptions about e-cigarette use during pregnancy based on an I ntegrated H ealth B elief M odel (IHBM). This paper describes the study design, methods, sample population and limitations of STEP. Methods Our sequential mixed methods study combined qualitative and quantitative approaches. In the qualitative section of the study which preceded the quantitative part of the study, we aimed to characterize risk perceptions about e-cigarette use during pregnancy. We used a netnographic research approach which analyzed discussion threads in online forums dealing with e-cigarette use during pregnancy. The analysis was based on an IHBM. Identified themes were incorporated in the questionnaire which was developed for the quantitative part of the study. The quantitative section aimed to quantify, among other things, perceived threats, barriers and benefits and to explore differences in risk perception according to sociodemographic characteristics and tobacco and e-cigarette usage. Results In the qualitative section, 1552 posts in 25 online discussion threads dealing, inter alia, with e-cigarette use during pregnancy were identified. The quantitative part looked at the responses in the questionnaires handed in by 575 pregnant women who attended a hospital in Hamburg (Germany) from April 2018 to January 2019 (response rate: 27.5%). Conclusion Data collection was successful for both the qualitative and quantitative parts of the study. When interpreting the results of STEP, different limitations should be taken into account. The results of STEP provide starting points for the development of tailored preventive measures for pregnant women., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Background: The preterm birth rate in Germany has remained unchanged at 8-9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care., Methods: This review is based on pertinent publications from the years 2000-2019 that were retrieved by a selective search in PubMed., Results: The clinical risk factors for preterm birth-known mainly from retrospective cohort studies-include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e., <25 mm in the second trimester (aOR: 6.9). In women with a short cervix, vaginally administered progesterone significantly lowers the preterm birth rate (22.5% vs. 14.1% for birth before 33 weeks of gestation, RR: 0.62; 95% confidence interval [0.47; 0.81]). Nicotine abstinence is associated with a lower pre- term birth rate as well (aOR: 0.91; [0.88; 0,.94]), while working more than 40 hours per week (aOR: 1.25; [1,.01; 1,.54]) and heavy lifting during pregnancy (hazard ratio [HR]: 1.43; [1.13; 1.80]) are associated with a higher preterm birth rate. Avoidance of physical exertion, or bed rest, in the face of impending preterm birth does not lower the preterm birth rate, but it does increase the risk of complications, such as thromboembolism., Conclusion: The meticulous assessment and elimination of treatable risk factors at the outset of ambulatory prenatal care can help lower the preterm birth rate. Further velopment of causally directed treat- ments (e.g., changes of relevant environmental and epigenetic factors).

Objective: Previous studies have shown that e-cigarettes are perceived as being less harmful than tobacco cigarettes by pregnant women and might be used to quit smoking during pregnancy. Our aim was to further explore and characterise perceived threats, benefits and barriers of e-cigarette use during pregnancy., Methods: Our STudy on E-cigarettes and Pregnancy (STEP) was, among others, based on a netnographic approach of analysing existing threads in German-speaking online discussion forums dealing with perceived threats and benefits of e-cigarette use during pregnancy. For the analysis, we used an inductive-deductive qualitative content analysis., Findings: Based on 25 online discussion threads containing 1552 posts, we identified perceived threats, perceived benefits and perceived barriers to e-cigarette use during pregnancy, among others, as main themes. Subthemes identified within the main theme perceived threats were severe nicotine related health risks, potential health risks of additional ingredients, relative risks and lack of knowledge and research studies. As perceived benefits, we identified possibility and facilitation of smoking cessation, harm reduction and financial benefits. Perceived barriers were lack of satisfaction and social stigma., Conclusion: Our qualitative results suggest that the perception of the health threats related to e-cigarette use during pregnancy varies according to the nicotine content and the perception of relative risks compared with tobacco cigarettes. In addition to this, risk perception is defined through further health and non-health related barriers and benefits (e.g. suitability of e-cigarettes as a smoking cessation aid, social stigma)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups., Methods: The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus)., Recommendations: Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes., Competing Interests: Die Interessenkonflikterklärungen aller Autoren finden Sie in der Langversion der Leitlinie., (© Georg Thieme Verlag KG Stuttgart · New York.)

This position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Aims: This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups., Methods: Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus)., Recommendations: Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth., Competing Interests: Die Interessenkonflikterklärungen aller Autoren finden Sie in der Langversion der Leitlinie., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: β 2 -sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β 2 -sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β 2 -mimetic tocolytic agents like fenoterol., Methods: Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups., Results: N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates < 32 weeks of gestation or with a birth weight < 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p < 0.005)., Conclusions: Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β 2 -sympathomimetic tocolytic drugs.

Preterm birth is one of the major global health problems and part of the Millennium Development goals because of the associated high number of perinatal or neonatal mortality and long-term risks of neurodevelopmental and metabolic diseases. Transvaginal sonography has meanwhile been established as a screening tool for spontaneous preterm birth despite its relatively low sensitivity when considering only the cervical length. Vaginal progesterone has been shown to reduce prematurity rates below 34 weeks in a screening population of singleton pregnancies. Up to now, no positive long-term effect could be demonstrated after 2 years. It seems to have no benefit to prolong pregnancies after a period of preterm contractions and in risk patients without cervical shortening. Meta-analyses still demonstrate conflicting results dependent on quality criteria used for selection. A cerclage is only indicated in singleton pregnancies with previous spontaneous preterm birth and a combined cervical shortening in the current pregnancy. Nevertheless, the short- and long-term outcome has never been evaluated, whereas maternal complications may be increased. There is no evidence for a prophylactic cervical cerclage in twin pregnancies even in cases with cervical shortening. Emergency cerclage remains an indication after individual counseling. The effect of a cervical pessary in singleton pregnancy seems to be more pronounced in studies where a few investigators with increasing experience have treated and followed the patients at risk for preterm birth. Mainly in twin pregnancies, pessary treatment seems to be promising compared to other treatment options of secondary prevention when the therapy is started at early stages of precocious cervical ripening. At present, several international trials with the goal to reduce global rates of prematurity are in progress which will hopefully allow to specify the indications and methods of intervention for certain subgroups. When trials are summarized, prospective meta-analyses carry a lower risk of bias than the meanwhile uncontrolled magnitude of retrospective meta-analyses with conflicting results.

Purpose: This is an official interdisciplinary guideline, published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG), the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking countries and is backed by the German Society of Anaesthesiology and Intensive Medicine (DGAI), the Society of Thrombosis and Haemostasis Research (GTH) and the German Association of Midwives. The aim is to provide a consensus-based overview of the diagnosis and management of peripartum bleeding obtained from an evaluation of the relevant literature., Methods: This S2k guideline was developed from the structured consensus of representative members of the various professional associations and professions commissioned by the Guideline Commission of the DGGG., Recommendations: The guideline encompasses recommendations on definitions, risk stratification, prevention and management.

Worldwide, post-partum haemorrhage (PHH) remains one of the leading causes for maternal mortality. The German Society of Gynaecology and Obstetrics, the German Midwifes' Society, the German Society of Thrombosis and Haemostasis and the German Society of Anaesthesiology and Intensive Care updated the former guideline. The resulting recommendations are the results of a structured literature search and a formal consensus process and contain all aspects of PPH including diagnosis, causes, risk factors and therapy. Key aspect of the anaesthesiological and haemostatic therapies is the development of an interdisciplinary standard operating procedure containing medical options related to the bleeding's cause and severity as well as the surgical option. For suspected PPH, this guideline emphasizes clinical and laboratory-based diagnostics, as only those will enable an early identification of the bleeding's causes and the resulting causative therapy. Recommendations cover evidence-based application of uterotonics for atony as well as tranexamic acid, calcium, factor concentrates and blood products. Additionally, recommendations are given on the topics of cell salvage, controlled hypotension and restrictive transfusion triggers., (© Georg Thieme Verlag Stuttgart · New York.)

Retroviral engineering of hematopoietic stem cell-derived precursor T-cells (preTs) opens the possibility of targeted T-cell transfer across human leukocyte antigen (HLA)-barriers. Alpharetroviral vectors exhibit a more neutral integration pattern thereby reducing the risk of insertional mutagenesis. Cord blood-derived CD34+ cells were transduced and differentiated into preTs in vitro. Two promoters, elongation-factor-1-short-form, and a myeloproliferative sarcoma virus variant in combination with two commonly used envelopes were comparatively assessed choosing enhanced green fluorescent protein or a third-generation chimeric antigen receptor (CAR) against CD123 as gene of interest. Furthermore, the inducible suicide gene iCaspase 9 has been validated. Combining the sarcoma virus-derived promoter with a modified feline endogenous retrovirus envelope glycoprotein yielded in superior transgene expression and transduction rates. Fresh and previously frozen CD34+ cells showed similar transduction and expansion rates. Transgene-positive cells did neither show proliferative impairment nor alteration in their lymphoid differentiation profile. The sarcoma virus-derived promoter only could express sufficient levels of iCaspase 9 to mediate dimerizer-induced apoptosis. Finally, the CD123 CAR was efficiently expressed in CD34+ cells and proved to be functional when expressed on differentiated T-cells. Therefore, the transduction of CD34+ cells with alpharetroviral vectors represents a feasible and potentially safer approach for stem cell-based immunotherapies for cancer.

Objective: to explore pregnant women's experiences with the recently implemented screening for gestational diabetes mellitus (GDM)., Design: qualitative study., Setting: Rhine-Neckar Metropolitan region, Germany., Participants: 20 pregnant women aged 27-41 years (mean: 32.6 years) who were at least in gestational week 29, i.e., those who should have already been screened for GDM., Measurements and Findings: semi-structured interviews with open-ended questions were conducted via telephone between November 2013 and February 2014. All interviews were audiotaped, transcribed verbatim and subsequently analyzed using qualitative content analysis according to Mayring. The screening was seen as an important instrument to detect GDM and thus to prevent possible health problems in both mother and child. Some deviations from the recommended screening procedure were reported in the interviews, e.g., collecting capillary blood instead of venous blood during an oral glucose tolerance test (OGTT); offering an OGTT without a prior glucose challenge test (GCT); conducting a GCT after an overnight fast. Two women had to actively ask for the screening to be done. One woman reported that her gynaecologist advised her against the screening., Conclusion and Implication for Practice: this qualitative study reflects the women's experiences with the new screening for GDM. Our findings show that two years after the introduction of universal GDM screening in Germany the screening procedure does not always seem to meet the standards of the German maternity guidelines., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Mother to infant transmission of hepatitis B virus (HBV) represents a major factor in maintaining chronic infection and depends on the degree of maternal infectivity status., Objectives: To examine the seroprevalence of hepatitis B virus surface antigen (HBsAg) in women at reproductive age admitted to the Department of Gynaecology at a German university hospital., Study Design: The seroprevalence of hepatitis B surface antigen (HBsAg) in 5518 women at reproductive age was examined, HBsAg-positive samples were tested for additional HBV markers to verify the infection status., Results: Out of 5518 samples from women at reproductive age, 88 women (1.59%) were positive for HBsAg and 7 of these HBV-positive women (7.95%) were additionally positive for HBeAg. The majority of the study population were German citizens, however most HBV infected persons originated from countries with a high HBV prevalence. The HBV seroprevalence in our study group is about two times higher compared to the average seroprevalence in the German citizen adult population, thus probably resulting in an underestimation of the infection rate in a multinational setting., Conclusions: Screening for HBsAg during pregnancy is still necessary and important for reduction of perinatal HBV transmission even in countries with low HBV prevalence.

The physiologic and pathologic changes of the uterine cervix during pregnancy leading to cervical ripening are not well understood though are related to the chief pathology and a commonly performed intervention in obstetrics: Preterm birth and labor induction. Normal cervical ripening is thought to be controlled by a variety of hormonal changes occurring during pregnancy leading to softening and dilation. Abnormal premature ripening, usually resulting in preterm labor, is thought to be associated with infection and inflammatory events. Despite many studies of the cervix, we still rely upon relatively crude methods for clinical evaluation of the cervix. In the past several years, we have developed and evaluated a method to measure cervical collagen noninvasively using an instrument called Collascope. Studies in animals and humans conducted in a variety of settings indicate that cervical function can be successfully monitored using the Collascope during pregnancy. We suggest that this technique might be useful to better define management in cases of spontaneous preterm and induced term cervical ripening.

This study examines the relationship between inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the control of cervical ripening and parturition under normal (normal term pregnancy) and abnormal (preterm labor and prolongation of pregnancy) conditions by (a) measuring changes in the collagen both visually and quantitatively, (b) localizing and characterizing iNOS and COX-2 under normal conditions, and (c) characterizing the changes in iNOS and COX-2 under abnormal conditions. Cervices are obtained from estrus and timed pregnant Sprague-Dawley rats (n=4-10 per group). Preterm labor is induced with Onapristone (3 mg/rat; progesterone antagonist) and the prolongation of pregnancy with progesterone (2.5 mg, twice daily). Collagen changes are measured and visualized with the picrosirius polarization method. RT-PCR is used to characterize the mRNA expression (p<0.05), and immunohistochemistry is used to localize the protein expression for iNOS and COX-2. The organization and birefringence of the collagen during pregnancy decreased and is supported by changes in the luminosity (p<0.001). The iNOS and COX-2 enzymes were localized in cervical smooth muscle, vascular smooth muscle, and epithelium. Under normal conditions, iNOS mRNA levels decreased as COX-2 mRNA levels increased demonstrating an inverse correlation (Spearman r = -0.497; p=0.00295). Onapristone stimulated preterm labor, increasing the iNOS and COX-2 mRNA (p<0.05). The increase demonstrated a positive correlation (Spearman r = 0.456; p=0.03). Progesterone prolonged pregnancy, decreasing the iNOS and COX-2 mRNA (p=0.036). In conclusion, there may be an interaction between the nitric oxide and prostaglandin pathways in cervical ripening and parturition.

Objective: To define the changes in cervical light-induced fluorescence (LIF), an index of cross-linked collagen, after the use of locally applied prostaglandin preparations for labor induction at term and the correlation between LIF and Bishop-Score., Study Design: The characteristic LIF of cervical collagen was measured from the surface of the cervix using a specially designed instrument (collascope) in 41 gravidas undergoing labor induction at term by prostaglandins. LIF and Bishop-Score were obtained directly before and 4h after the administration of prostaglandin. Paired Student's t-test, Wilcoxon Signed Rank test, Linear Regression, Spearman correlation and Fisher Exact test were used as appropriate., Results: Cervical LIF decreased significantly after prostaglandin application (0.982+/-0.04 [before] to 0.885+/-0.037 [after], p=0.025). The decrease in LIF correlated with the initial LIF before PG-application (r=0.61). The Bishop-Score increased in all 41 patients. No correlation was found between LIF versus Bishop-Score., Conclusions: Cervical application of prostaglandins decreases the amount of cross-linked collagen as measured by LIF. This effect was observed only in patients with a prior high cross-linked collagen.

Background and Purpose: The increasing use of systemic adjuvant therapy even in lymph node-negative breast cancer patients and breast cancer screening programs detecting smaller tumors with less probability of metastatic lymph nodes questions the need for routine axillary lymph node dissection. Since morbidity of breast cancer surgery is predominantly related to axillary lymph node dissection, predictive models for lymph node involvement may provide a way to avoid lymph node surgery and its side effects in subgroups of patients., Patients and Methods: Using a multivariate logistic regression model, tumorbiological parameters such as expression of estrogen and progesterone receptors, Ki-67, p53, cathepsin D, HER2, S-phase fraction, and ploidy were analyzed regarding their ability to predict axillary lymph node involvement in 655 breast cancer patients., Results: The model correctly predicted axillary lymph node metastases in 58% of the patients by including expression of progesterone receptor, HER2, and Ki-67. In a subgroup of 200 patients predicted to be at extremely high or extremely low risk for axillary lymph node metastases, the accuracy of the prediction was 70%., Conclusion: With a model just based on tumorbiological parameters obtained in the primary tumor it is possible to predict axillary lymph node status. By including additional parameters it appears to be feasible to further improve the model in order to avoid axillary lymph node surgery in low-risk women.

Background: Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term., Methods: The three isomers of NOS--inducible (iNOS), endothelial (eNOS) and neuronal (bNOS)--were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups., Results: Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent., Conclusion: The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

Studies in animals and humans indicate that uterine performance can be successfully monitored during pregnancy using uterine electromyography. Uterine electromyography could be used to better define management in a variety of conditions associated with human labor. The potential benefits of the proposed instrumentation and method include: reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean-section rate, and providing research methods to better understand uterine function.

Objective: The purpose of this study was to determine whether the platelet-activating factor antagonist WEB-2170 inhibits preterm cervical ripening induced by lipopolysaccharide or by antiprogestin RU 486., Study Design: Timed-pregnant rats were killed on day 16 after treatment with (1) WEB-2170, lipopolysaccharide, lipopolysaccharide plus WEB-2170, or vehicle control and (2) with WEB-2170, RU 486, RU 486 plus WEB-2170, or vehicle control. Cervical ripening was assessed by light-induced fluorescence and resistance to stretch. Statistics were assessed by 1-way analysis of variance followed by Tukey-test (P <.05)., Results: Light-induced fluorescence and resistance to stretch were significantly lower in the lipopolysaccharide-treated and in the RU486-treated animals compared with vehicle control (lipopolysaccharide:light-induced fluorescence, 7.0+/-0.6 vs 12.8+/-0.8 [P=.001]; resistance to stretch, 0.41+/-0.03 N/mm vs 0.54+/-0.04 N/mm [P <.05]; RU486:light-induced fluorescence, 9.6+/-0.6 vs 11.7+/-0.6 [P <.05]; resistance to stretch, 0.28+/-0.06 N/mm vs 0.61+/-0.02 N/mm [P <.001]). Compared with vehicle control, WEB-2170 alone did not alter cervical light-induced fluorescence or resistance to stretch. Although WEB-2170 significantly blocked cervical ripening after lipopolysaccharide administration (light-induced fluorescence, 11.3+/-1.3 [P <.05]; resistance to stretch, 0.61+/-0.04 [P <.01]), WEB-2170 did not inhibit the RU 486-induced cervical ripening., Conclusion: Although infection-related cervical ripening is inhibited by platelet-activating factor antagonists, the physiologic process of cervical ripening appears to be unaffected. Platelet-activating factor inhibition may be of clinical value in the infection-related pathologic processes that are responsible for premature cervical ripening.

Objectives: This study was undertaken to evaluate the effect of proteinase-activated receptor-2 (PAR-2) activation on the contractility of uterine tissues from term pregnant rats and the role of mast cells and prostaglandins in such an effect., Study Design: Uterine rings from pregnant (day 20-21) Sprague-Dawley rats were used for isometric tension recording in organ chamber experiments (Krebs solution, 5% carbon dioxide in air, 37 degrees C, pH approximately 7.4). Responses to the PAR-2 activating peptide SLIGRL (serine-leucine-isoleucine-glycine-arginine-leucine), and to the inactive reverse peptide LRGILS (leucine-arginine-glycine-isoleucine-leucine-serine) were determined after pretreatments with compound 48/80, cromolyn, S[+]-chlorpheniramine maleate, cimetidine, combinations of histamine (H) receptor antagonists with cromolyn or ibuprofen and compared with vehicle., Results: SLIGRL significantly augmented contractility of uterine tissues, and this response was not inhibited by compound 48/80, cromolyn, and ibuprofen, as well as by H(1)- and H(2)-receptor antagonists, alone or in combination with cromolyn., Conclusion: PAR-2 activation augments uterine contractility in tissues obtained from term pregnant rats, and this effect is independent of mast cell activation or cyclo-oxygenase pathway products.

Objective: The purpose of this study was to investigate gestational changes of cervical light-induced fluorescence, an index of cross-linked collagen, and the relationship between light-induced fluorescence and the time-to-delivery interval., Study Design: Fifty patients were included in one of two groups. (1) Twenty-one healthy pregnant women without signs of labor underwent repeated cervical light-induced fluorescence measurement during the last trimester. (2) Light-induced fluorescence was measured in 29 patients with signs of labor, and the time from measurement to delivery was noted. Cervical light-induced fluorescence was obtained noninvasively with a prototype instrument that was designed specifically for this purpose. Spearman correlation and the Student t test and receiver-operator characteristics analysis were performed (P <.05)., Results: Light-induced fluorescence correlated negatively with gestational age and positively with time-to-delivery interval, was significantly lower in patients who were delivered <24 hours compared with those patients who were delivered >24 hours later, and was predictive of delivery within 24 hours., Conclusion: Cervical light-induced fluorescence decreases significantly as gestational age increases. Light-induced fluorescence may be a useful tool to identify patients in whom delivery is imminent.

Objective: The purpose of this study was to determine the effect of locally applied platelet-activating factor on cervical ripening and leukocyte infiltration., Study Design: Timed-pregnant rats were treated vaginally twice each day on days 14 and 15 of gestation with platelet-activating factor 5 x 10(-8) mol/L (low-dose), 5 x 10(-7) mol/L (high-dose), or solvent and were killed on day 16. Cervical ripening was assessed by cervical resistance-to-stretch and light-induced autofluorescence of cross-linked collagen. Longitudinal sections of the cervix were hematoxylin and eosin stained, and the number of polymorphonuclear leukocytes in eight high-power fields was determined., Results: Cervical resistance-to-stretch and light-induced autofluorescence were decreased in rats that were treated with high-dose platelet-activating factor compared with controls (0.4375 +/- 0.0126 N/mm vs 0.5528 +/- 0.0294 N/mm, and 2.739 +/- 0.150 N/mm vs 3.475 +/- 0.236 N/mm; P <.05). High-dose platelet-activating factor led to infiltration with polymorphonuclear leukocytes compared with control (22.1 +/- 5.2 vs 2.1 +/- 1.3 cells/8 high-power fields, P <.05)., Conclusion: Local platelet-activating factor application induces cervical ripening accompanied by stromal polymorphonuclear leukocyte infiltration. Platelet-activating factor may play a major role in parturition under physiologic and pathologic conditions.

Objective: To investigate the content of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and interleukin-8 messenger ribonucleic acid (mRNA) in the lower uterine segment during term parturition., Study Design: mRNA extracts from the lower uterine segment obtained from 53 women undergoing non-elective caesarean section at term were analyzed by semi-quantitative reverse transcriptase polymerase chain reaction. The patients were grouped according to cervical dilatation (less than 2 cm, n=18; 2 to less than 4 cm, n=13; 4-6 cm, n=7; more than 6 cm, n=15) at the time of caesarean section., Results: Interleukin-1 beta and interleukin-8 mRNA-contents at more than 6 cm cervical dilation were significantly higher than at less than 2 cm. The levels of interleukin-6 were already significantly increased in the 4-6 cm group, while the tumor necrosis factor alpha ribonucleic acid content did not change during parturition., Conclusion: The process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment. These findings support the theory that the activation of the inflammatory network plays an important role in the progress of cervical dilatation.

Aims: To determine interleukin (IL)-6 and IL-8 concentrations in the lower uterine segment in patients with chorioamnionitis compared to those without., Methods: Biopsy specimens from the lower uterine segment of 33 patients with chorioamnionitis were matched to specimens of 33 patients without. The biopsies had been taken during cesarean section. The concentrations of IL-6 and IL-8 in protein extracts of these specimens were determined by enzyme linked immunosorbent assays., Results: Compared to the controls patients with chorioamnionitis showed significantly lower gestational age and higher parity, and were more likely to receive fenoterol or betamethasone. In the chorioamnionitis group the median IL-6 concentrations were higher than in the controls (61.5 and 19.4 pg/mg protein, respectively [p < 0.01]). The same applies to the median IL-8 concentrations (162.3 and 13.4 pg/mg protein, respectively [p < 0.001])., Conclusions: To our knowledge this is the first study which could clearly demonstrate significantly increased IL-6 and IL-8 levels in the lower uterine segment of patients with chorioamnionitis. Increased concentrations of pro-inflammatory cytokines may play a pivotal role in cervical softening and dilatation during chorioamniotic infection.