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BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has had dramatic effects on the pregnant population worldwide, increasing the risk of adverse perinatal outcomes. OBJECTIVE: To assess the incidence of antepartum stillbirth (aSB) during the COVID-19 pandemic in Austria. METHODS: We collected epidemiological data from the Austrian Birth Registry and compared the rate of aSB (i.e., fetal death at or after 24+0 gestational weeks) during the pandemic period (March-December 2020) and in the respective pre-pandemic months (2015-2019). RESULTS: In total, 65 660 pregnancies were included, of which 171 resulted in aSB at 33.7 ± 4.8 gestational weeks. During the pandemic, the aSB rate increased from 2.49‰ to 2.60‰ (P = 0.601), in contrast to the significant decline in preterm deliveries at or before 37 gestational weeks from 0.61‰ to 0.56‰ (relative risk [RR] 0.93; 95% confidence interval [CI] 0.91-0.96; P

Preterm birth remains the major cause of death and disability among children under the age of five. In developing countries antenatal preterm birth prevention clinics are set up to provide cervical length surveillance and/or treatment modalities such as cerclage or progesterone for those women with identified risk factors such as previous cervical treatment or preterm birth. However, 85% of women have no risk factors for PTB and currently there is no biomarker to screen women early in pregnancy. Women will present unexpectedly in threatened preterm labour and we have no choice but to adopt a re-active approach to their care by using predication and preparation strategies such as fetal fibronectin, tocolytic therapy and steroids. Despite these strategies approximately 15-20% of these women will give birth preterm before 34 weeks. There is a urgent need to re-design primary, secondary and tertiary prevention strategies for spontaneous preterm labour (sPTL) in singleton pregnancies aimed at identifying and addressing key gaps in clinical practice and research.

The use of drugs in pregnancy always raises concerns regarding potential fetal exposure and possible adverse effects through their accumulation in fetal tissues and organs. Barusiban is an oxytocin antagonist under development for potential use as tocolytic in preterm-labor patients. It displays greater affinity for the oxytocin receptor compared to vasopressin V1A receptor and would thus not interfere with vasopressin-induced effects of the V1A receptor. Barusiban placental transfer was determined in the rabbit and cynomolgus monkey and in an ex vivo human cotyledon model. In the rabbit, there was an approximately 5% transfer of barusiban from the maternal to the fetal blood, without significant accumulation in any of the investigated fetal tissues. In the cynomolgus monkeys, the mean fetal plasma barusiban concentration was 9.1% of the maternal level. This was similar to the percentage of barusiban transfer in the human placental single cotyledon, which once equilibrated ranged between 9.3 and 11.0% over the observation period. The transfer of the small-molecule antipyrine as a comparator in this human model was approximately three times greater. The similarity in the degree of transfer in the cynomolgus monkey and human cotyledon, while being less in the rabbit, may reflect the species-specific placental barrier structure between the maternal and fetal compartments. In conclusion, limited placental transfer of barusiban occurred in all three models. The similarity of barusiban transfer in the cynomolgus and the human placental single cotyledon suggests the latter ex vivo model to be useful in assessing future drug candidates to be used in pregnant women., Limited barusiban placental transfer occurred in all three models, with the similarity of transfer in the cynomolgus and the human cotyledon, suggesting this ex vivo model to be useful in assessing human placental transfer of pharmaceuticals.

Objectives Twin pregnancies have a higher likelihood to experience spontaneous preterm birth (PTB). Those with imminent PTB need to be determined in order to undergo fetal lung maturation with glucocorticoids and therewith improve neonatal outcomes. The aim of this study was to assess the predictive value of the fetal fibronectin (fFN) test and the measurement of cervical length in twin pregnancies with symptoms of imminent PTB. Study design We performed an observational study on all twin pregnancies at the Medical University Vienna. Women were admitted to the hospital either due to symptoms of imminent PTB or due to a shortening of the cervical length before completed 34 weeks of gestational age. Logistic regression analysis was performed to assess the predictive value of the fFN test and cervical length on imminent preterm birth. Results The data of 82 women with twin pregnancies were eligible, of which 10 (12 %) had a positive, 45 (55 %) a negative, 21 (26 %) an unclear fFN result, and 6 (7 %) showed missing data. Cervical length ≤20 mm did not show any statistical significant prediction of PTB in our study cohort. After 7 days, 4/10 (40 %) pregnant women with positive fFN test gave birth, while 4/45 (9 %) women with a negative fFN test gave birth. Within 14 days after hospitalization, 6/10 (60 %) women with a positive fFN test gave birth, compared to 4/45 (9 %) with a negative fFN test. The positive fFN test was a statistically significant predictor of PTB within 7 days (p = 0.02) and 14 days (p = 0.004), respectively. Conclusion The fFN test has the potential to detect women with twin pregnancies, who are at risk of giving birth within the following days. Hence, the practice of hospitalizing women solely due to the shortening of the cervical length cannot be supported.

Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria.Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population.The implementation of a universal GDM screening program in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

Zusammenfassung Ziel Offizielle Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (ÖGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG). Ziel der Leitlinie ist es, die Prädiktion, die Prävention und das Management der Frühgeburt anhand der aktuellen Literatur, der Erfahrung der Mitglieder der Leitlinienkommission einschließlich der Sicht der Selbsthilfe evidenzbasiert zu verbessern. Methoden Anhand der internationalen Literatur entwickelten die Mitglieder der beteiligten Fachgesellschaften und Organisationen Empfehlungen und Statements. Diese wurden in einem formalen Prozess (strukturierte Konsensuskonferenzen mit neutraler Moderation, schriftliche Delphi-Abstimmung) verabschiedet. Empfehlungen Der Teil 2 dieser Kurzversion der Leitlinie zeigt Statements und Empfehlungen zur tertiären Prävention der Frühgeburt sowie zum Management des frühen vorzeitigen Blasensprungs.

This overview analyzes the data on the controversial therapy of iron substitution during pregnancy, the diagnosis of iron deficiency anemia and the indication-related therapy, and is the first recommendation issued by the OEGGG on the appropriate therapy. The effects of anemia during pregnancy on postnatal outcomes have been intensively investigated with heterogeneous results. A final scientific conclusion with regards to the "optimal" maternal hemoglobin level is limited by the heterogeneous results of various studies, many of which were conducted in emerging nations (with different dietary habits and structural differences in the respective healthcare systems). The current literature even suggests that there may be a connection between both decreased and increased maternal serum hemoglobin concentrations and unfavorable short-term and long-term neonatal outcomes. In Austria, 67 percent of pregnant women take pharmacological supplements or use a variety of dietary supplements. Clinically, the prevalence of maternal anemia is often overestimated, leading to overtreatment of pregnant women (iron substitution without a medical indication). To obtain a differential diagnosis, a workup of the indications for treatment should be carried out prior to initiating any form of iron substitution during pregnancy. If treatment is medically indicated, oral iron substitution is usually sufficient. Because of the restricted approval and potential side effects, medical indications for intravenous iron substitution should be limited. Intravenous iron substitution without a prior detailed diagnostic workup is an off-label use and should only be used in very limited cases, and women should be advised accordingly.

The aim of this prospective study (Clinical Trials Identifier: NCT02993744) was to detect the effect of fetal lung maturation with betamethasone on the maternal inflammatory parameters C-reactive protein (CRP) and leukocytes. The blood results of 75 patients in the week of gestation (WOG) 23/0 to 34/6 under threat of preterm delivery and treated with betamethasone were analyzed. Sixty-five pregnant women without complications served as control group. Leukocyte numbers increased significantly about 2.4 thsd./µL (±3.3 standard deviation), with a confidence interval of 95% from 1.5 to 3.2 (

Zusammenfassung Ziel Offizielle Leitlinie der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), der Österreichischen Gesellschaft für Gynäkologie und Geburtshilfe (ÖGGG) und der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe (SGGG). Ziel der Leitlinie ist es, die Prädiktion, die Prävention und das Management der Frühgeburt anhand der aktuellen Literatur, der Erfahrung der Mitglieder der Leitlinienkommission einschließlich der Sicht der Selbsthilfe evidenzbasiert zu verbessern. Methoden Anhand der internationalen Literatur entwickelten die Mitglieder der beteiligten Fachgesellschaften und Organisationen Empfehlungen und Statements. Diese wurden in einem formalen Prozess (strukturierte Konsensuskonferenzen mit neutraler Moderation, schriftliche Delphi-Abstimmung) verabschiedet. Empfehlungen Der Teil I dieser Kurzversion der Leitlinie zeigt Statements und Empfehlungen zur Epidemiologie, Ätiologie, der Prädiktion sowie der primären und sekundären Prävention der Frühgeburt.

Introduction Starting from the second trimester of pregnancy, passive immunity is provided to the human fetus by transplacental transfer of maternal IgG. IgG transfer depends on the neonatal Fc receptor, FcRn. While FcRn localization in the placental syncytiotrophoblast (STB) has been demonstrated unequivocally, FcRn expression in placental-fetal endothelial cells (pFECs), which are part of the materno-fetal barrier, is still unclear. Therefore, this study aimed to elucidate the spatio-specific expression pattern of FcRn in placental tissue. Methods FcRn expression was investigated by western blotting in term placentas and in isolated human placental arterial and venous endothelial cells (HPAEC, HPVEC) using a validated affinity-purified polyclonal anti-peptide antibody against the cytoplasmic tail of FcRn α-chain. In situ localization of FcRn and IgG was studied by immunofluorescence microscopy on tissue sections of healthy term placentas. Results FcRn expression was demonstrated in placental vasculature particularly, in HPAEC, and HPVEC. FcRn was localized in cytokeratin 7+ STB and in CD31+ pFECs in terminal as well as stem villi in situ. Additionally, CD68+ placental macrophages exhibited FcRn expression in situ. Endogenous IgG partially co-localized with FcRn in STB, pFECs, and in placental macrophages. Discussion Placental FcRn expression in endothelial cells and macrophages is analogous to the expression pattern in other organs. FcRn expression in pFECs suggests an involvement of FcRn in IgG transcytosis and/or participation in recycling/salvaging of maternal IgG present in the fetal circulation. FcRn expression in placental macrophages may account for recycling of monomeric IgG and/or processing and presentation of immune complexes.

COVID-19 is placing considerable strain on healthcare systems. Disaster and military medicine specialists were involved in the outbreak in Italy, after many units were overwhelmed. Health providers were caught off guard and personnel was unprepared to face this unprecedented threat. Local decisions accelerated the rate of the spread. Many countries declared a state of emergency and lockdown to contain the exponential transmission of the disease. The purpose of this review is to suggest quick key points of strategies to implement in obstetric units without delay to respond to the oncoming wave, based on experience and feedback from the field. It is essential in an emergency situation to understand what is at stake and prepare maternity wards in the best possible way.

INTRODUCTION: Globally, preterm birth has replaced congenital malformation as the major cause of perinatal mortality and morbidity. The reduced rate of congenital malformation was not achieved through a single biophysical or biochemical marker at a specific gestational age, but rather through a combination of clinical, biophysical and biochemical markers at different gestational ages. Since the aetiology of spontaneous preterm birth is also multifactorial, it is unlikely that a single biomarker test, at a specific gestational age will emerge as the definitive predictive test. METHODS: The Biomarkers Group of PREBIC, comprising clinicians, basic scientists and other experts in the field, with a particular interest in preterm birth have produced this commentary with short, medium and long-term aims: i) to alert clinicians to the advances that are being made in the prediction of spontaneous preterm birth; ii) to encourage clinicians and scientists to continue their efforts in this field, and not to be disheartened or nihilistic because of a perceived lack of progress and iii) to enable development of novel interventions that can reduce the mortality and morbidity associated with preterm birth. RESULTS: Using language that we hope is clear to practising clinicians, we have identified 11 Sections in which there exists the potential, feasibility and capability of technologies for candidate biomarkers in the prediction of spontaneous preterm birth and how current limitations to this research might be circumvented. DISCUSSION: The combination of biophysical, biochemical, immunological, microbiological, fetal cell, exosomal, or cell free RNA at different gestational ages, integrated as part of a multivariable predictor model may be necessary to advance our attempts to predict sPTL and PTB. This will require systems biological data using "omics" data and artificial intelligence/machine learning to manage the data appropriately. The ultimate goal is to reduce the mortality and morbidity associated with preterm birth.

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.

(1) Background: Across Europe, the incidence of antepartum stillbirth varies greatly, partly because of heterogeneous definitions regarding gestational weeks and differences in legislation. With this study, we sought to provide a comprehensive overview on the demographics of antepartum stillbirth in Austria, defined as non-iatrogenic fetal demise ≥22+0 gestational weeks (/40). (2) Methods: We conducted a population-based study on epidemiological characteristics of singleton antepartum stillbirth in Austria between January 2008 and December 2020. Data were derived from the validated Austrian Birth Registry. (3) Results: From January 2008 through December 2020, the antepartum stillbirth rate ≥20+0/40 was 3.10, ≥22+0/40 3.14, and ≥24+0/40 2.83 per 1000 births in Austria. The highest incidence was recorded in the federal states of Vienna, Styria, and Lower and Upper Austria, contributing to 71.9% of all stillbirths in the country. In the last decade, significant fluctuations in incidence were noted: from 2011 to 2012, the rate significantly declined from 3.40 to 3.07‰, whilst it significantly increased from 2.76 to 3.49‰ between 2019 and 2020. The median gestational age of antepartum stillbirth in Austria was 33+0 (27+2–37+4) weeks. Stillbirth rates ≤26/40 ranged from 164.98 to 334.18‰, whilst the lowest rates of 0.58–8.4‰ were observed ≥36/40. The main demographic risk factors were maternal obesity and low parity. (4) Conclusions: In Austria, the antepartum stillbirth rate has remained relatively stable at 2.83–3.10 per 1000 births for the last decade, despite a significant decline in 2012 and an increase in 2020.

Objective: To compare PAMG-1 and phIGFBP-1 tests in predicting impending spontaneous preterm delivery within 7 days upon presentation in pregnant women with symptoms of preterm labor. Study Design: From September 2014 to April 2015 women with singleton gestation, symptoms of preterm labor, GA 22 - 35, participated in this prospective cohort study upon admission. Recruited patients had intact membranes and a minimal cervical dilatation of ≤3 cm. Vaginal swabs for phIGFBP-1 and PAMG-1 were taken in addition to routine treatment. Biochemical test results were blinded and had no effect on management of patients. Results: A total of 96 patients were screened for inclusion into the trial; 57 met the inclusion criteria for final analysis. The PAMG-1 test was positive in 5.7% of patients, while phIGFBP-1 test was positive in 29.8% of patients. The prediction of spontaneous preterm delivery within 7 days of admission in patients with a cervical length < 25 mm (30%), the PAMG-1 test and phIGFBP-1 test showed a SN of 100% and 100%; SP of 83.3% and 50.0%, (p ≤ 0.05); PPV of 71.4% and 45.5%; and NPV of 100% and 100%. 89.5% of women who received corticosteroids and 84.2% of women who received tocolysis did not go into preterm labor within one week. Conclusion: Our study supports the high negative predictability of biochemical tests to rule out spontaneous preterm labor in patients with a short cervix. However, our study strongly suggests that the PAMG-1 test is more accurate for predicting imminent spontaneous preterm delivery as compared to phIGFBP-1. These findings can significantly reduce economic burden caused by unnecessary admission and treatment of patients suspected of preterm labor. Such a reduction in the use of corticosteroids and tocolytics would lead to a reduction in the short and long term health effects associated with the use of therapeutic drugs like corticosteroids, antibiotics and tocolytics.

Preterm neonates display an impaired vaccine response. Neonatal antigen-presenting cells (APCs) are less effective to induce an adaptive immune response and to promote the development of immunological memory. Efficient adjuvantal toll-like receptor (TLR)-triggering may overcome the neonatal immunological impairment. Accordingly, the aim of this study was to investigate the immunostimulatory action of R-848 and CpG-B on neonatal APCs. Surface marker and cytokine secretion of APCs were evaluated after incubation of cord blood and peripheral blood mononuclear cells with the indicated adjuvants and were analyzed using flow cytometry. TLR-specific stimulation resulted in a significant induction of costimulatory molecules on neonatal APCs. Stimulation with R-848 resulted in significant higher secretion of TNFα, IL-6, IL-10, IL-12/IL-23p40, IL-12p70, and IFN-γ. Interestingly, CpG-B resulted in significant higher secretion of TNFα and IL-6. In summary, the incubation of TLR-agonists induced activation and maturation of neonatal APCs. These data show that modern TLR-specific adjuvants achieve a direct effect and potent upregulation of activation and maturation markers and cytokines in preterm neonates. We thus conclude that agents triggering TLRs might possibly overcome neonatal lack of vaccine responses.

Purpose To determine the incidence of gestational diabetes mellitus (GDM) in pregnant women who received vaginal progesterone due to short cervical length or to prevent recurrent preterm birth. Methods In this retrospective study, we included 190 women with singleton pregnancies at risk for preterm birth who received vaginal natural progesterone (200 mg daily between gestational weeks 16 + 0 and 36 + 0) for a minimum of 4 weeks and delivered > 28 weeks. The control group consisted of 242 age- and body mass index (BMI)-matched patients without progesterone administration. Data were acquired from a database containing prospectively collected information. Patients with pre-existing diabetes, and conception after in vitro fertilisation procedure were excluded. Results The incidence of GDM did not differ significantly between the progesterone-treated and the control group (14.7% vs. 16.9%, respectively; p = 0.597). In a binary regression model, patients with higher pre-pregnancy BMI (OR 1.1; p = 0.006), and those with a family history of diabetes had a higher risk for GDM development (OR 1.8; p = 0.040), whereas vaginal progesterone treatment had no significant influence (p = 0.580). Conclusion The use of vaginal progesterone for the prevention of recurrent preterm delivery and in women with a short cervix does not seem to be associated with an increased risk of GDM.

These guidelines are based upon most recent and updated evidence and they are adapted to a European perspective by an expert view of the problem. These guidelines are not intended to be a meta-anal...

The purpose of this guideline is to provide a decision aid for diagnosis, treatment, and follow-up of patients with major perineal tears and thus minimize the risk of persistent symptoms. In 2007, the "Guideline for the management of third and fourth degree perineal tears after vaginal birth" was established by members of the Austrian Urogynecologic Working Group (AUB). The guideline was updated in 2011, including literature published up to 30 November 2011. The DELPHI method was used to reach consensus. Evidence-based and consensus-based statements were defined for epidemiology, risk factors, classification, diagnosis, surgery, and follow-up of major perineal lacerations at vaginal birth.

Lung MRI volumetrics may be valuable for fetal assessment following early preterm premature rupture of the foetal membranes (pPROM).To evaluate the predictive value of MRI lung volumetrics after pPROM.Retrospective cohort study of 40 fetuses after pPROM in a large, tertiary, perinatal referral center. Fetuses underwent MRI lung volumetrics. Estimated lung volume was expressed as percentage of expected lung volume (our own normal references). Primary outcome was neonatal mortality due to respiratory distress before discharge from hospital.Gestational age range was 16-27 weeks. Estimated-to-expected lung volume was 73% in non-survivors and 102% in survivors (P0.05). There were no survivors with a lung volume less than 60% of expected. By logistic regression, mortality could be predicted with a sensitivity of 80%, specificity of 86% and accuracy of 85%.Fetal MR lung volumetrics may be useful for predicting mortality due to respiratory distress in children with early gestational pPROM.

Objective: In consideration of comprehensive and well-established vaccination programmes in industrialized countries, it is expected that immunity against tetanus among expectant mothers and their offspring is complete. Our study evaluated seroprotection against tetanus among newborns in Austria, who may gain passive immunity by transplacental transfer of maternal tetanus antibody. Methods: Cord blood samples from 99 deliveries were analyzed for antibody concentration against tetanus toxoid by standardized ELISA. Results: 85/99 (85.8%) individuals presented with levels of tetanus immunity having a protective antibody concentration ≧0.1 IU/ml. 9/99 (9.1%) samples showed low seropositivity, while in 5/99 (5.1%) samples no tetanus antibodies could be detected. The median antibody concentration was 0.95 IU/ml. Conclusions: Our data provide evidence for a lack of adequate tetanus immunity in 14.2% of newborns delivered in an Austrian University Hospital. This investigation is emphasizing the importance of stringent regimens concerning prenatal vaccination care, even in countries with generalized immunization programs. If indicated, maternal immunization during pregnancy should be initiated for protection of newborns.

Calcium channel blockers (CCBs) are not licensed for use in pregnancy but are used without robust surveillance to treat hypertension in pregnancy and preterm labour. The objective of this study was to evaluate the fetomaternal safety of CCB in pregnancy by a quantitative systematic review.Medline (1996-2005), EMBASE (1996-2003), BIOSIS (1993-2003), Current contents (1995-2003), DERWENT DRUGFILE (1983-2003) and Cochrane Library (2005: issue 3). The number of women reporting an adverse event was used to compute a percentage of the total number of women in whom the occurrence of that event or confirmation of its absence was reported. Meta-regression with generalised estimation equations modelling explored reasons for heterogeneity, seeking factors that increased the rates of the most commonly reported adverse events.Of 269 relevant reports, including 5607 women, adverse fetomaternal events varied according to the total dose of nifedipine and study design. Adverse events were highest amongst women given more than 60 mg total dose of nifedipine [odds ratio (OR) 3.78, 95% confidence interval (CI) 1.27-11.2, p = 0.017] and in reports from case series compared to controlled studies (OR 2.45, 95% CI 1.17-5.15, p = 0.018).Adverse event rates generated from this study provide an evidence base for clinical guidelines and informed patient consent for CCB use in pregnancy.

Objective To investigate the influence of culture proven intrauterine infection on preterm morbidity and to test the effect of antimicrobial treatment. Methods Retrospective cohort study conducted between October 1997 and February 2001 in patients with preterm premature rupture of membranes or preterm labor. Vaginal swabs were sampled and amniocentesis for microbiologic culture of the amniotic fluid was performed. Patients with Ureaplasma urealyticum in the amniotic fluid were treated with josamycin. Infants were followed post partum according to birth weight, gestational age, APGAR score and infant morbidity. Results In 49 eligible patients, 40% of cultures were positive, 22% for Ureaplasma urealyticum, 12% for other bacteria and 6% for candida. Children of mothers with positive amniotic fluid cultures had significantly lower gestational ages (26 + 4 weeks for Ureaplasma urealyticum [ p = 0.04] and 25 + 5 weeks for other microorganisms [ p = 0.0017] versus 28 + 6 weeks for mothers with negative amniotic fluid cultures) and lower birth weights (975 g [n.s.] and 828 g [ p = 0.0072] versus 1041 g) but were appropriate for their gestational ages. 33.3% and 66.7% versus 24% of the children were mechanically ventilated [n.s.], duration of mechanical ventilation was 5.3 [ p = 0.02] and 10.1 days [ p = 0.04] versus 1.4 days, and prevalence of chronic lung disease was 38% and 33% versus 11% [n.s.]. Prevalence of severe intraventricular hemorrhage (12.5% [n.s.] and 33% [ p = 0.04] versus 3.4%) and nosocomial infections (50% for both groups of positive cultures versus 10.3% for negative cultures, p = 0.02 and 0.03, respectively) was higher and median length of stay was significantly longer (121 [ p = 0.02] and 107 days [ p = 0.03] versus 60 days) in these patients. Maternal positive vaginal swab cultures were not associated with any of the above-mentioned factors. In none of the patients treated with macrolids for proven Ureaplasma urealyticum amnionitis could the microbes be eradicated. Conclusion Maternal positive amniotic fluid cultures have been associated with lower gestational age and lower birth weight. Rate of infant morbidity was higher and length of stay was significantly longer in this group. Positive vaginal swabs were not predictive for infant morbidity. Treatment of mothers showing positive amniotic fluid cultures with macrolids was not effective.

Recent evidence from the literature suggested that hCG preparations purified from urine of pregnant women, which are widely used in in vitro studies and IVF programs, may contain contaminants such as EGF. To determine the putative biological effects of the contaminating growth factor, we here investigated distinct trophoblast differentiation processes in the presence of various hCG compounds. Western blot analyses indicated that treatment of trophoblastic SGHPL-5 cells and purified term trophoblasts with potentially EGF-contaminated hCG (hCG-A) resulted in auto-phosphorylation of the EGF receptor at tyrosine 1173 whereas supplementation of another urine-purified hCG preparation (hCG-B), recombinant holo-hCG or recombinant αhCG had no effects. Phosphorylation was specifically blocked by the EGF receptor inhibitor PD153035. Urinary hCG-A was most effective in promoting invasion of SGHPL-5 cells through Matrigel-coated transwells, but increased invasiveness was also observed in the presence of hCG-B or recombinant holo-hCG. Similarly, the extent of syncytialisation of term trophoblasts, quantitated by nuclei in desmoplakin-negative areas, was highest upon addition of hCG-A or recombinant EGF as a control. PD153035 reduced invasion and fusion of trophoblasts supplemented with hCG-A, but did not diminish the effects provoked by hCG-B. In conclusion, the data suggest that the EGF contamination of hCG considerably affects trophoblast function. Experiments using EGF-free hCG preparations demonstrate that the hormone increases trophoblast invasion and syncytialisation.

A well-organized interplay between many molecular factors as well as mechanical forces influence fetal lung development. At the end of this complex process a sufficiently sized and structurally mature organ should ensure the postnatal survival of the newborn. Besides prenatal ultrasonography, magnetic resonance imaging (MRI) can now be used to investigate normal and pathological human lung growth in utero. Oligohydramnios, due to premature rupture of membranes (PROM), is an important risk factor for compromised fetal lung growth. In these situations MR volumetry can be used to measure the size of the fetal lung quite accurately. Together with the evaluation of lung signal intensities on T2-weighted sequences, fetuses with pulmonary hypoplasia can be readily detected.

Expression of the trophoblast-specific subunit of human chorionic gonadotropin, CGbeta, is associated with fusion of cytotrophoblasts into a multinuclear syncytium. Here, we studied regulation of the CGbeta5 gene in trophoblasts undergoing in vitro syncytialization. Transfection of luciferase reporters harboring different lengths of the CGbeta5 upstream sequence revealed that the proximal promoter region (-345 to +114) is sufficient to govern differentiation-dependent induction. Mutational analyses suggested that two selective promoter factor (Sp) and three activating protein 2 (AP-2) recognition sequences are necessary for full activity of the promoter. During syncytialization these elements interacted with increasing amounts of the transcription factors Sp1, Sp3, and AP-2alpha in electrophoretic mobility shift assay, but only AP-2alpha binding rose upon elevation of cAMP levels with forskolin. Increasing expression of different isoforms of Sp1 and Sp3 could also be detected by Western blot analyses. Sp1/Sp3 localized to syncytial nuclei both in differentiated cultures and in term placental tissue, suggesting assembly of functional transcriptional complexes. Costaining of the transcription factors with E-cadherin on term placental sections revealed that 47 and 33% of cytotrophoblast nuclei were negative for Sp1 and Sp3, respectively. In contrast, immunohistochemistry of early tissue demonstrated expression of Sp1 in the majority of cyto- and syncytiotrophoblasts, whereas Sp3 was absent from the syncytium. Sp1 and Sp3 induced wild-type/mutant promoter constructs upon transfection in Sp-deficient SL-2 cells, indicating that the Sp elements function as activating sequences. The data suggest that increasing concentrations of Sp1, Sp3, and AP-2alpha enhance transcription of CGbeta in differentiating term trophoblasts, whereas a different combination of factors may control expression in early placentas.

Introduction: Oxytocin receptors (OTR) and gap junctions (GJ) represent key factors in the development and expansion of regular uterine contractions. Its concentrations in human myometrium rise with increasing gestational age which leads to higher sensitivity for peripheral oxytocin and raising contractility. The aim of this study was to compare the density of GJ formation with the OTR concentration during the course of pregnancy. Material and Methods: Tissue samples were obtained in cesarean sections for various reasons from transverse incisions in the lower uterine segment. Five representative groups of patients were defined: 1. preterm delivery w/o labor (n=3), 2. preterm delivery with labor (n = 6), 3. term delivery w/o labor (n = 7), 4. term delivery with labor (n = 7), 5. term, failed induction of labor with oxytocin (n = 5). OTR concentrations were investigated by saturation experiments using the method of Soloff and Alexandrova. The frequency and fractional percentage of membrane occupied by GJ was obtained using electronmicroscopy and photography. Results: OTR concentrations rose to peak values in early term and preterm labor. The frequency and fractional area of GJ was low and similar in all groups although a nonsignificant trend to lower areas was observed in preterm samples. There was no correlation between OTR concentrations and GJ. OTR density, but not GJ frequency or areas, were positively correlated with the frequency of uterine contractions. OTR concentrations in samples from patients at term and after failed oxytocin induction did not differ significantly from samples at term w/o labor. Conclusions: A rise in OTR, but not in GJ, was associated with the onset of labor. It can be concluded that this increase in OTR density in the lower uterine segment is of higher importance for the onset of labor both in preterm and term labor than the rise of GJ formations.

We studied the production of the oxytocin receptor and interleukins in human uterine smooth muscle cells cultured in vitro in the presence of cytokines that were shown to be elevated in gestational diseases such as intrauterine infections and chorioamnionitis.Human uterine smooth muscle cells were cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS). Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After 6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from total RNA using quantitative, competitive reverse transcriptase-polymerase chain reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from supernatants after 6, 12, 24, and 48 hours of stimulation by commercially available enzyme-linked immunosorbent assay.In nonstimulated cultures basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL-1beta induced a statistically significant decrease in oxytocin receptor mRNA abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6 and IL-8 release, whereas secretion of the two interleukins was not altered in the presence of LPS or hypoxia. Expression of IL-1beta was not significantly induced under inflammatory or hypoxic culture conditions.The constitutive and cytokine-inducible expression of interleukins from uterine smooth muscle cells suggests that the myometrium may contribute to the overall production of inflammatory mediators in the uterus that are thought to govern term- or infection-induced preterm labor. Down-regulation of the oxytocin receptor under IL-1beta in myometrial cells may indicate that initiation and maintenance of labor could be partially limited under severe inflammatory conditions such as chorioamnionitis.

Infektionen, Aktivierung der Inflammationskaskaden, Uberdehnung des Uterus, Fehlbildungen des Uterus, mutterlicher Stress sowie verschiedene Formen der Plazentapathologie sind die Hauptursachen von spontanen Fruhgeburten. Davon abzugrenzen sind die medizinisch indizierten Fruhgeburten nach einer indizierten Schwangerschaftsbeendigung wegen mutterlicher oder fetaler Pathologie.

Purpose: To evaluate the effects of Atosiban which has been recently made available for routine treatment of patients with threatening pre-term delivery. Advantage of this tocolytic drug is its specific action on reproductive tissues. Material and Methods: 79 Patients were retrospectively evaluated, diagnoses at admission were pre-term labor (50), pre-term rupture of membranes (21), vaginal bleeding (6) and incompetent cervix (6). Gestational age lied between 21st and 33rd week of pregnancy. Pre-term labor was defined as >4 uterine contractions/30 min and at least one of these 2 examinations positive: 1. cervical length

Die postpartale Blutung zahlt zu den Hauptursachen der Muttersterblichkeit auch in der westlichen Welt. Neben etablierten Leitlinien ist der Nutzen standardisierter Therapiealgorithmen belegt. Ein Therapiealgorithmus fur den geburtshilflichen Notfall «Postpartale Hamorrhagie» fehlte bisher im deutschsprachigen Raum.

L’hemorragie postpartale figure parmi les causes majeures de mortalite maternelle, meme dans le monde occidental. A part les directives etablies, la valeur d’algorithmes therapeutiques standardises est confirmee. Un tel algorithme pour l’urgence obstetricale «hemorragie postpartale» manquait jusqu’ici pour les germanophones.

Differentiation of primary villous cytotrophoblasts into syncytia is associated with increasing production of α and β human CG subunits, which is predominantly governed at the level of messenger RNA expression. Here, we present a detailed study on the mechanisms involved in the differentiation-dependent regulation of the trophoblast-specific CGα gene promoter. Site-directed mutations in each of the five DNA-elements of the composite enhancer were performed to investigate the contribution of the individual regulatory sequences to the overall transcriptional activity of the promoter at two different stages of trophoblast in vitro differentiation. We show that deletion of one cyclic AMP response element (CRE) did not affect CGα promoter activity in cytotrophoblasts; however, it reduced transcription by 33% in differentiating cultures. Removal of both CREs almost abolished transcription at early and later stages of in vitro differentiation. Upon mutation the enhancer elements αACT, JRE, and CCAAT significantl...

Objective: Our purpose was to compare concentrations of messenger ribonucleic acid specific for the oxytocin receptor and for the vasopressin 1a receptor in myometrial and endometrial tissues of pregnant and nonpregnant women. Study Design: Tissues from pregnant uteri were obtained from 95 women who were undergoing cesarean delivery between 26 and 42 weeks' gestation. Tissues from nonpregnant uteri were obtained from 7 cycling women who were undergoing hysterectomy. The competitive reverse-transcription polymerase chain reaction method was used to determine messenger ribonucleic acid concentrations. Results: A significant increase in oxytocin receptor messenger ribonucleic acid was found during the first half of pregnancy. Oxytocin receptor messenger ribonucleic acid concentrations were lower in tissues with spontaneous contractions than in quiescent tissues and were decreased in patients with advanced labor. Vasopressin 1a receptor messenger ribonucleic acid concentrations were high in tissues from both cycling and pregnant uteri but remained unchanged throughout gestation. Conclusion: The increase in oxytocin receptor protein concentrations seen in pregnancy is only partially controlled by messenger ribonucleic acid abundance. High concentrations of vasopressin 1a receptor messenger ribonucleic acid confirm the biologically active role of this receptor in both the cycling and the pregnant uterus. (Am J Obstet Gynecol 1998;179:1572-8.)

The majority of drugs that are used today for tocolysis have been developed for clinical conditions other than preterm labour. Obstetricians started to use these drugs as tocolytics because of their additional influence on uterine smooth muscle relaxation, accepting their cardiovascular (side) effects. Because the majority of these drugs are used off label, today's strict criteria to evaluate drugs for their predominant use in pregnancy have not been applied; therefore, we also lack sufficient peri- and neonatal follow up data for these drugs. This problem is compounded as our understanding of the regulation of myometrial smooth muscle contraction and relaxation is still incomplete.

Functionality and morphology of pDCs of preterm newborns, with emphasis on TLR9 triggered IFN-α production. Bacterial and viral infections cause high rates of morbidity and mortality in premature newborns. In the setting of viral infection, pDCs play a key role as strong producers of IFN-α upon TLR9 activation. We analyzed pDC frequency, phenotype, morphology, and function in CB of preterm and term newborns in comparison with adults. Whereas all age groups show similar pDC numbers, BDCA-2, CD123, and TLR9 levels, the expression of BDCA-4 and capacity to produce IFN-α upon TLR9 challenge were decreased significantly in preterm neonates. Furthermore, we show by means of electron microscopy that pDCs from preterm newborns exhibit a distinct, “immature” morphology. Taken together, these findings suggest decreased functionality of pDCs in the premature newborn. The reduced capacity to produce IFN-α is likely to render such infants more susceptible to viral infections.

Detrusor instability is the second most common cause of femal urinary incontinence. Oxybutynin chloride anticholinergic action with direct muscle-relaxant properties. 39 women with persistent-urgeincontinence participated in a pilot study of intravesical oxybutynin application. Patients received either 20 mg oxybutynin or placebo as 40 ml sterile sodium chloride solution administered intravesically over a period of 10 days. Urodynamic assessment as well as micturition protocols were performed before and after treatment. The intravesical oxybutynin-application was significantly better than the placebo application concerning reduction of pollakisuria and nycturia. Oxybutynin also increased bladder capacity more than in the placebo-treated group (p < 0.01) and provided an improvement of bladder compliance (p < 0.05). No local or systemic side effects were observed which would have immediately terminated the oxybutynin treatment.

The purpose of this retrospective study is to evaluate the effects of atosiban (Tractocile available in Austria since February 2000) for routine treatment of women with threatened preterm delivery. The advantage of this drug compared to other tocolytic agents is its specific action on reproductive tissues without the accompanying severe side effects. Women (n = 208) were retrospectively evaluated. Diagnoses at admission were preterm labour (n = 117), preterm rupture of membranes (n = 65), incompetent cervix (n = 19) and vaginal bleeding (n = 7). Gestational age was between weeks 21 and 33 of pregnancy. Preterm labour was defined as/=4 uterine contractions/30 min and cervical length30 mm examined by vaginal ultrasound and/or detection of vaginal fetal fibronectin. Tocolytic effectiveness was determined as the number of women having a diagnosis of preterm labour who were still pregnant after 48 hours and after 7 days. The influence on the frequency of contractions before and 3-12 hours after the start of treatment was assessed. Maternal side effects, perinatal and neonatal morbidity and transfers to the NICU were also evaluated. The proportion of women who remained undelivered was 78.7% after 48 hours, and 64.3% after 7 days. Atosiban decreased the frequency of contractions from 5.4/30 min before treatment to 1.6 contractions/30 min after the start of treatment. At the initial bolus application, 20.2% of women presented drug-related side effects, such as nausea, vertigo and flush over a short period of 1-2 minutes. During infusion, side effects possibly related to atosiban could be detected in 6% of women. Mean length of stay was 11.8 days in the NICU and 30.9 days in intermediate care. Twenty-three children developed intraventricular haemorrhage (I-IV). In conclusion, atosiban is an effective tocolytic drug in the treatment of preterm labour and preterm rupture of the membranes. It has significantly less side effects due to its lack of cardiovascular activity.

It is internationally agreed that diabetes mellitus (DM) is associated with increased maternal and fetal morbidity and long-term complications. To avoid these complications, it is often necessary to induce birth before term. The impact of DM on spontaneous preterm birth (spontaneous labor, preterm premature rupture of membranes and/or cervical incompetence resulting in delivery before the completion of 37 gestation weeks) is still unexplained. Preterm birth accounts for the most neonatal deaths and infant morbidities, and therefore it still remains one of the biggest challenges in obstetrics.Our study determined if there is an increasing tendency towards spontaneous preterm birth in mothers with gestational and preexisting DM.In this retrospective cohort study, 187 pregnant women with gestational DM and preexisting DM were compared to a randomized control group consisting of 192 normoglycemic women concerning gestational age and perinatal outcome. Data were collected by the Medical University of Vienna. Multiple pregnancies and women with severe maternal diseases, such as preeclampsia, were excluded.Women with DM tended significantly more often to preterm births (P = 0.002). A significant difference in the incidence of spontaneous preterm birth was found (P = 0.047).DM affects the length of gestation and incidence of spontaneous preterm birth.