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We present a case with an incidental finding of abnormal cardiotocography (CTG) pattern as well as elevated middle cerebral artery peak systolic velocity (MCA-PSV) in an otherwise inconspicuous pregnancy. Massive fetomaternal hemorrhage (FMH) was detected as the cause by flow cytometry (FC), resulting in multiple cycles of fetal blood sampling (FBS) showing severe anemia, intrauterine transfusions (IUTs), a preterm delivery, and a healthy infant in follow-up examinations., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Accidental hypothermia in mature neonates requiring hospitalization is a clinical complication that has not been studied in detail. In the present study, the effect of accidental hypothermia on common morbidity in neonates in the postnatal period was investigated. We did temperature measurements in 616 mature neonates after birth, after transfer to the maternity ward and at check-up at age of 48-72 hours of life. Additionally, nurses checked temperature until discharge at every diaper change in 302 of all included neonates who were small for gestational age (SGA) or whose mothers had green fluid or premature rupture of membranes (PROM). We investigated if there was a correlation between infection, hyperbilirubinemia, hypoglycemia, SGA, gestational diabetes, PROM, green amniotic fluid, positive GBS status of the mother, and accidental hypothermia in the first 48-72 hours of life. Mature neonates showed transient accidental hypothermia in the first 24 hours of life. No significant correlation between infection (p=0.571), hyperbilirubinemia (p=0.837), hypoglycemia (p=0.072), and accidental hypothermia could be seen. There was a significant correlation between SGA (p=0.020), PROM (p=0.008), and accidental hypothermia, while hyperthermia was associated with infection (p=0.009) and green amniotic fluid (p=0.004). SGA and PROM represent perinatal risk factors for postnatal transient accidental hypothermia in mature neonates. Increased morbidity or mortality associated with postnatal accidental hypothermia has not been demonstrated.Akzidentelle Hypothermie bei Reifgeborenen, die einer Hospitalisierung bedürfen, ist eine bisher nicht näher analysierte klinische Komplikation. In der vorliegenden Arbeit wurde die Abhängigkeit einer akzidentellen Hypothermie von typischen Erkrankungen der Postnatalperiode untersucht. Wir führten bei 616 Reifgeborenen Temperaturmessungen nach Geburt, nach Verlegung auf die Wochenstation und bei der Vorsorgeuntersuchung U2 durch. Zusätzlich kontrollierten wir bei 302 der 616 Neugeborenen mit Small for gestational age (SGA), grünem Fruchtwasser oder vorzeitigem Blasensprung (PROM) die Temperatur bei jedem Windelwechsel bis zur Entlassung. Wir untersuchten, ob es einen Zusammenhang zwischen Infektion, Hyperbilirubinämie, Hypoglykämie, SGA, Gestationsdiabetes, PROM, grünem Fruchtwasser, positivem GBS-Status der Mutter und akzidenteller Auskühlung innerhalb der ersten 48-72 Lebensstunden gab. Reifgeborene zeigten in den ersten 24 Lebensstunden transiente akzidentelle Hypothermien. Es konnte kein signifikanter Zusammenhang zwischen Infektion (P=0.571), Hyperbilirubinämie (p=0.837), Hypoglykämie (p=0.072) und akzidenteller Hypothermie festgestellt werden. Es bestand ein signifikanter Zusammenhang zwischen SGA (p=0.020), PROM (p=0.008) und akzidenteller Hypothermie, während Hyperthermie war mit Infektion (p=0.009) und grünem Fruchtwasser (p=0.004) assoziiert war. SGA und PROM stellen perinatale Risikofaktoren für postnatale transiente, akzidentelle Hypothermien bei Reifgeborenen dar. Eine erhöhte Morbidiät bzw. Mortalität im Zusammenhang mit postnataler akzidenteller Hypothermie konnte nicht nachgewiesen werden., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The non-classical human leucocyte antigen (HLA) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern that depends on fetal sex. HLA-G expression was analysed in a total of 80 placentas (40 placentas from women with GDM and 40 healthy controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS). Double immunofluorescence staining identified the cells expressing HLA-G in the decidua and allowed evaluation of the expression pattern. We found a significant (p < 0.001) reduction of HLA-G expression in extravillous cytotrophoblasts (EVTs) in the placentas of women with GDM as compared to the healthy controls and were able to demonstrate that this downregulation was not due to a loss of cell number, but to a loss of expression intensity. A special change in the cell pattern of EVTs was observed, with these cells showing an obvious decrease in HLA-G expression on their cell surface. No significant differences according to fetal sex were found. These data show a possible association between decreased HLA-G expression and presence of GDM and provide new insights into altered placental function in women with GDM., (© 2022. The Author(s).)

Competing Interests: Lecture fees and/or consulting services: Hummel – Astra Zeneca, Boehringer-Ingelheim, Dexcom, Lilly, MSD, Novo Nordisk, Sanofi; Füchtenbusch – Abbott, Astra Zeneca, Berlin Chemie, Boehringer, Glaxo Smith Kline, Lilly, Novo Nordisk, Sanofi; Bührer – Chiesi, Nestlé; Battefeld – Berlin Chemie, Lilly, Novo Nordisk; Groten – Novo Nordisk, JenaPharm; Haak – Abbott, AstraZeneca, MSD, Roche; Kainer – GE Canon; Kautzky-Willer – Novo Nordisk, Lilly, Boehringer Ingelheim, AstraZeneca, Sanofi, Amgen, Novartis; Meissner – Lilly, Novo Nordisk; Nagel-Reupner – Amgen, Boehringer, Novo Nordisk, MSD, Lilly; Schäfer-Graf – Novo Nordik, Sanofi, Berlin-Chemie; Siegmund – Abbott, Astra, Berlin Chemie, Boehringer, Lilly, Medronic, MSD, Novo Nordisk, Roche, Sanofi

Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10 - 0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour., 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/ ).)

Purpose: Chlamydial genital infections constitute significant sexually transmitted infections worldwide. The often asymptomatic status of C. trachomatis (CT) infections leads to an increased burden on human reproductive health, especially in middle- and low-income settings. Early detection and management of these infections could play a decisive role in controlling this public health burden. The objective of this review is to provide an insight into the evolution of diagnostic methods for CT infections through the development of new molecular technologies, emphasizing on -omics' technologies and their significance as diagnostic tools both for effective patient management and control of disease transmission., Methods: Narrative review of the diagnostic methodologies of CT infections and the impact of the introduction of -omics' technologies on their diagnosis by review of the literature., Results: Various methodologies are discussed with respect to working principles, required specifications, advantages, and disadvantages. Implementing the most accurate methods in diagnosis is highlighted as the cornerstone in managing CT infections., Conclusion: Diagnostics based on -omics' technologies are considered to be the most pertinent modalities in CT testing when compared to other available methods. There is a need to modify these effective and accurate diagnostic tools in order to render them more available and feasible in all settings, especially aiming on turning them to rapid point-of-care tests for effective patient management and disease control., (© 2021. The Author(s).)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Competing Interests: The authors declare that they have no conflict of interest.

Background: The quality guideline for care delivery to preterm and mature infants (QFR-RL) places high demands on perinatal centers. In this analysis, the degree of fulfillment was determined. Additionally, care delivery to further patient groups and sufficient nursing staff capacity for care delivery to imminent preterm infants (FG) were evaluated., Methods: A network of 4 perinatal centers (level 1) with about 10,000 births per year supplied the data on the ratio of 1:1/1:2-care infants, patients per nurse, and nursing staff capacity. This data was statistically evaluated by center, shift, and week day over a period of 5 months for compliance with QFR-RL and DGPM recommendations. Furthermore, imminent preterm infants were recorded and compared with available nursing staff capacity., Results: In total, the QFR-RL was fulfilled in 88% of shifts (n=1,584). Only one center reached the required 95%. The degree of fulfillment and the number of staff nurses declined from late to night shifts (p<0.001). The ratio of 1:1-care infants was significantly higher when demands were not fulfilled (p<0.001). Only 14.1% of imminent preterm infants could have been attended in accordance with the QFR-RL., Conclusion: 1:1 care as well as lower nurse staffing in late and night shifts lead to non-fulfillment of requirements and poorer care delivery to other intensive care patients. This was also reflected in the lower degree of fulfillment of DGPM recommendations. Sufficient nursing staff capacity was rare with the consequence that it was almost impossible to deliver care to imminent preterm infants per the guideline., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Thyroid hormones are essential for development of trophoblasts and the fetus. They also regulate a wide range of metabolic processes. We investigated the influence of maternal gestational diabetes mellitus (GDM) on thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 of the human placenta in a sex- and cell-type specific manner. Term placental tissue was obtained from women with (n = 40) or without GDM (control; n = 40). THRs levels were measured by semi-quantitative immunohistochemistry and real-time qRT-PCR. We localized THR immunostaining in syncytiotrophoblast (SCT), which was the tissue with the strongest signal. Double immunofluorescence identified THR in decidual cells in the stroma and in extravillous cytotrophoblasts. GDM did not change THRα1 immunolabelling intensity in decidua, but was associated with a stronger immunolabelling in SCT compared to GDM ( p < 0.05). The SCT difference of GDM vs. control was strongest ( p < 0.01) in female placentas. THRα2 was only weakly present and immunolabelling was weaker ( p < 0.05) in SCT of only male GDM placentas in comparison to male controls. THRβ1/β2 immunostaining was weak in all cell types without changes in GDM. However, more THRβ1/2 protein was present ( p < 0.001) in male than female placentas. All these protein changes were paralleled by changes of THR transcript levels. The data show that THR are expressed in term trophoblast in relation to fetal sex. Maternal GDM influences predominantly THRα1 in SCT, with the strongest GDM effect in SCT of female placentas.

Introduction: Antenatal betamethasone administration in the context of foetal lung maturity enhancement has a transient impact on the short-term variation (STV) of the foetal heart rate. There are currently various algorithms for computing the STV, each one resulting in different STV values. We studied the results of betamethasone administration on the STV using 2 different algorithms in order to investigate whether the effects of steroids on the STV depend on the algorithm used or not., Materials and Methods: In the context of a larger, single-centre, prospective, observational study, we gathered CTG traces under and without the influence of steroids in order to study their effect on the STV using 2 different computational algorithms (STV240 and STV16)., Results: A total of 285 CTGs were registered and subsequently analysed with both algorithms. When compared to the STV240 and STV16 without or at least 72 h after the first intramuscular corticosteroid administration, a transient increase of both the STV240 and STV16 was documented in the first 24 h, followed by a transient decrease of both the STV240 and STV16 between 24 h and 72 h after the first intramuscular corticosteroid injection., Conclusion: Our results confirmed that betamethasone administration has a transient but significant effect on the STV independently of the algorithm used. These observations stress once again the fact that a decreased STV within the first 72 h after maternal bethametasone administration should not be an indication for early delivery., Competing Interests: Christina Kouskouti declares paid consultancy from Philips Medizinsystem Böblingen in the past. All other autors declare no relevant conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.

Aims: Currently one of the most widespread systems for the computerized analysis of the fetal heart rate (FHR) is the Dawes-Redman system, where the short-term variation (STV) of the FHR is measured by dividing each minute into 16 segments (STV16). Technical progress has allowed for the development of a new algorithm, which measures the STV by dividing each minute into 240 segments (STV240), thus approximating the beat-to-beat variation. The STV240 still lacks reference values. Our aim was to develop clinically relevant reference values for the STV240 and compare them to the ones for the STV16., Methods: In a single centre, observational study, a total of 228 cardiotocograms were registered and subsequently analyzed with both algorithms (STV240 and STV16)., Results: The 95% confidence interval (CI) was calculated for both algorithms. The values of the STV240 were significantly lower in comparison to the ones of the STV16. Not only the mean values but also the 95th percentile of the STV240 lay beneath the existent cut-off value for the STV16., Conclusions: Every clinician using the new algorithm must be aware that the normal values for the STV240 lie beneath the, up until now, established cut-off values for the STV16.

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.

Purpose: Maternal sepsis remains one of the leading causes of direct and indirect maternal mortality both in high- and low-income environments. In the last two decades, systems biology approaches, based on '-omics' technologies, have started revolutionizing the diagnosis and management of the septic syndrome. The scope of this narrative review is to present an overview of the basic '-omics' technologies, exemplified by cases relevant to maternal sepsis., Methods: Narrative review of the new '-omics' technologies based on a detailed review of the literature., Results: After presenting the main 'omics' technologies, we discuss their limitations and the need for integrated approaches that encompass research efforts across multiple '-omics' layers in the '-omics' cascade between the genome and the phenome., Conclusions: Systems biology approaches are revolutionizing the research landscape in maternal sepsis. There is a need for increased awareness, from the side of health practitioners, as a requirement for the effective implementation of the new technologies in the research and clinical practice in maternal sepsis.

Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental parts and exerts a variety of functions in physiologic pregnancy. It regulates decidualisation and implantation, influences hormone secretion and placental immune modulations. This review highlights the role of the vitamin D receptor in physiologic and disturbed pregnancy, as preeclampsia, fetal growth restriction, gestational diabetes and preterm birth. We discuss the existing literature regarding common VDR polymorphisms in these pregnancy disorders., Competing Interests: The authors declare no conflict of interest.

Timely recognition and appropriate management of high-risk pregnancies, such as intrauterine growth restriction (IUGR), are of paramount importance for every obstetrician. After the initial screening of IUGR fetuses through sonographic fetometry and Doppler, the focus is shifted to the appropriate monitoring and timing of delivery. This can, especially in cases of early IUGR, become a very difficult task. At this point, cardiotocography (CTG) is introduced as a major tool in the day-to-day monitoring of the antenatal well-being of the IUGR fetus. Since the first introduction of CTG up to the nowadays widely spreading implementation of computerised CTG in the clinical practice, there has been great progress in the recording of the fetal heart rate, as well as its interpretation. Focus of this review is to offer an understanding of the evolution of CTG from its early development to modern computerised methods and to provide an insight as to where the future of CTG is leading, especially in the monitoring of IUGR.

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.)

Introduction: Monoamniotic twins are considered a cause of high-risk pregnancies. Thereby, discordant malformations do occur rarely. A discordant exencephaly has been described in only a few cases. Transcervical embryoscopy can be performed in cases of monoamniotic twins with missed abortion directly before the abort-curettage., Case Report: The case of a 35-year-old G1/P0 women in the 12(th) week of pregnancy is described. She had a monoamniotic twin pregnancy with discordant exencephaly and missed abortion diagnosed at 11+2 weeks. A transcervical embryoscopy was performed immediately before the abort-curettage and identified the discordant exencephaly and an additional umbilical cord knot of the 2 foetuses as a probable cause for the abortion., Discussion: The transcervical embryoscopy lead in our case report to the diagnosis of a umbilical cord knot in a monoamniotic twin pregnancy with missed abortion. We also identified a discordant exencephaly by embryoscopy. With blunt access to the amniotic cavity, the transcervical embryoscopy applies only a minor additional risk to the abort-curettage. However, it should only be performed when the patient explicitly asks for enhanced diagnostics., Conclusion: Transcervical embryoscopy can be performed as an additional diagnostic tool in cases of monoamniotic twins with missed abortion. However, a detailed risk-benefit analysis should be done upfront in consultation with the patient., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes., Study Design: Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter., Results: Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM., Conclusion: Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM., (© The Author(s) 2015.)

Purpose: Since the routine screening program for cervical dysplasia by Pap smear was established in the early 1970s, the rate of cervical cancer has continually dropped. Even if a high percentage of cervical dysplasia shows spontaneous restitution, the only effective therapy for persisting cervical dysplasia is local ablation or excision which might be associated with an increased risk of preterm delivery in subsequent pregnancies. However, data from German patients are missing, so the aim of this study was to evaluate the risk of preterm delivery and associated risks in a cohort of patients who had undergone cervical conisation previous to their pregnancies., Methods: A total of 144 patients with conisation and subsequent pregnancy were identified. They were compared regarding week of delivery and preterm birth, fetal birth weight, fetal outcome and birth procedure (spontaneous delivery, vacuum extraction, primary and secondary cesarean section) with their matched partners., Results: 135 patients with singleton pregnancies and their matched partners were evaluated in the final analysis. The mean age was 33.5 years. Comparing the case and control group we reached significant different results for week of delivery, but not preterm birth defined as birth prior to 37 weeks of gestation., Conclusions: Within this German cohort cervical conisation did not increase the risk for preterm birth, cesarean section or poor fetal outcome. We therefore conclude that cervical conisation is an appropriate method to treat women with cervical dysplasia also at childbearing age when prevention of cervical cancer is needed.

Objective: Gestational diabetes mellitus (GDM) is often accompanied by low maternal vitamin D, that is, calcitriol (1,25[OH]2 vitamin D3), levels. Here, we tested the hypothesis that the placental vitamin D receptor (VDR) is regulated by calcitriol and altered in GDM with distinct changes in different placental cell types. Specifically, we aimed to localize VDR in human term placentas from normal and GDM pregnancies, to quantify its cellular expression and to study in vitro its regulation by its physiological agonist calcitriol., Study Design: Placental tissue slides of 80 patients (40 with GDM/40 controls) were double stained for VDR and human leukocyte antigen G to identify extravillous trophoblasts (EVTs). Staining intensity was semiquantified. Quantitative real time-polymerase chain reaction and Western blotting measured VDR messenger RNA (mRNA) and protein in decidual tissue. The trophoblast cell line BeWo was used to study in vitro VDR regulation by calcitriol (0.01, 0.1, and 1 nmol/mL)., Results: Vitamin D receptor protein and mRNA levels are upregulated (P < .05) in EVT (1.8-fold) as well as in placental endothelium (5.8-fold) of patients with GDM. Expression of VDR is regulated by calcitriol in a bimodal manner: high doses (0.1 and 1 nmol/mL) caused downregulation, whereas the low dose (0.01 nmol/mL) resulted in VDR upregulation., Conclusion: Vitamin D receptor is upregulated in EVT and endothelium of GDM placentas. This could be due to low maternal vitamin D levels in patients with GDM because in vitro low calcitriol doses upregulate VDR in trophoblast cells., (© The Author(s) 2014.)

Aims: Peroxisome proliferator-activated receptor-gamma (PPARγ) plays an important role in insulin metabolism, trophoblast differentiation and anti-inflammatory circuits. The aim of this study was to investigate the expression of PPARγ in the placenta of patients with gestational diabetes mellitus (GDM) and the regulation of PPARγ by its agonists in trophoblast tumour cells BeWo in vitro., Methods: PPARγ expression in a total of 80 placentas (40 GDM/40 controls) was analysed by immunohistochemistry using the semi-quantitative immunoreactive score. Furthermore, a quantitative reverse transcription-polymerase chain reaction (PCR) was performed to determine the PPARγ mRNA-expression in both groups. We used a fused and a non-fused BeWo cell culture model for the stimulation with arachidonic acid and 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Afterwards PPARγ mRNA-expression was analysed by quantitative real-time PCR (RT-PCR) (TaqMan)., Results: Using immunohistochemistry we identified a decreased expression of PPARγ in the syncytiotrophoblast and the extravillous trophoblast of GDM placentas compared to normal controls. Furthermore, PPARγ mRNA-expression was reduced in GDM placentas. Stimulation of BeWo cells with arachidonic acid and 15d-PGJ2 caused a downregulation of PPARγ expression., Conclusion: As PPARγ is down regulated by arachidonic acid and 15d-PGJ2, the reduced PPARγ expression in GDM placentas may be due to an altered concentration of fatty acid derivates.

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

Purpose: Pro-inflammatory immunity, either infectious or sterile-derived, is one of the major causes of preterm birth and associated with enhanced maternal and fetal morbidity and mortality. Diagnosing intrauterine inflammation at an early stage is tremendously important. Amniotic fluid interleukin (IL)-6 concentration is currently the most investigated diagnostic tool for detecting intrauterine inflammation., Methods: Amniotic fluid samples were obtained from women with no signs of intrauterine infection [amniocentesis (n = 82), cesarean section (n = 110), spontaneous delivery (n = 20) and those with clinical signs of intrauterine infection or inflammation (AIS, n = 16)]. Amniotic fluid was screened by commercial ELISAs for IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, growth regulated oncogene-α (gro) α, macrophage inflammatory protein (MIP) 1α, MIP1β, histone, tumor necrosis factor (TNF) α, proIL1β and interferon γ-induced protein (IP) 10., Results: ProIL-1β, MIP1β, IL-10 and IL-8 levels were significantly elevated in the AIS group, whereas IL-4 levels were significantly lower in the AIS group. No significant differences were found regarding IL-2, IL-6, IL-12, IL-15, IL-17, GROα, MIP1α, histone, TNFα, ProIL1β and IP10., Conclusion: MIP1β, IL-4, IL-8, IL-10 and proIL-1β might be potential singular biomarkers in diagnosing intrauterine inflammation. The combinations of elevated levels of IL-17/GROα, MIP1β/IL-15 and histone/IL-10 are new potentially advantageous biomarker combinations.

Objective: Teaching intrapartum care is one of the most challenging tasks in undergraduate medical education. High-fidelity obstetric simulators might support students' learning experience. The specific educational impact of these simulators compared with traditional methods of model-based obstetric teaching has not yet been determined., Study Design: We randomly assigned 46 undergraduate medical students to be taught using either a high-fidelity simulator or a scale wood-and-leather phantom. Their self-assessments were evaluated using a validated questionnaire. We assessed obstetric skills and asked students to solve obstetric paper cases., Main Outcome Measures: Assessment of fidelity-specific teaching impact on procedural knowledge, motivation, and interest in obstetrics as well as obstetric skills using high- and low-fidelity training models., Results: High-fidelity simulation specifically improved students' feeling that they understood both the physiology of parturition and the obstetric procedures. Students in the simulation group also felt better prepared for obstetric house jobs and performed better in obstetric skills evaluations. However, the two groups made equivalent obstetric decisions., Conclusion: This study provides first data on the impact of high-fidelity simulation in an undergraduate setting.

Background: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated., Findings: Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age., Conclusion: Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.

This review focuses on the examination of the fetal brain, using three-dimensional (3D) ultrasound and the multiplanar rendering mode (MPR). The routine examination of the brain is achieved with axial planes but a dedicated fetal neurosonogram requires additional coronal and sagittal views, in order to provide a complete view of the different brain structures. Because these planes are difficult to obtain under many conditions, the present paper shows how 3D MPR allows one to obtain 1 or multiple reconstructed images from a digital volume. The display can be either as orthogonal planes, tomographic planes with parallel slices or as one single plane of the region of interest, which can be selected by the examiner. This approach allows easily the demonstration of the corpus callosum, the cerebellar vermis, the three-horn view, the foetal hippocampus and other regions. In addition, early neurosonography of the developing brain from the 7th week of pregnancy onwards can be achieved., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Fetomaternal hemorrhage (FMH) poses an immediate risk to the fetus and, in case of Rhesus-immunization, to future pregnancies. Given that altered endothelial permeability is part of the pathophysiology of inflammation, in this study we investigated whether placental inflammatory processes like chorioamnionitis (ChoA) or preeclampsia (PE) lead to increased rates of FMH compared to the established risk factor of placenta previa (PP). Putative accompanying markers of trophoblastic damage were also explored., Methods: 40 patients (14 PE; 6 ChoA; 9 PP; 11 normal controls) were evaluated for FMH using a flowcytometric test kit, which is able to quantify FMH of 0.06% fetal cells. Placental tissue samples were immunostained for human placental lactogen (hPL), human chorionic gonadotropin (hCG), and mucin-1 (MUC1). MUC1 was evaluated as a potential serum marker of FMH., Results: Patients with ChoA had a mean calculated FMH volume of 29 ml, compared to 4 ml in PE and 1 ml in PP and controls. MUC1 staining was reduced in PE and ChoA placenta samples, while elevated MUC1 serum concentration correlated positively with FMH., Conclusion: Diseases of placental inflammation are associated with FMH. Placental MUC1 staining is reduced and serum concentrations are increased in cases of FMH.

Objective: The crucial first step in the prevention of mother-to-child transmission of HIV is awareness of pregnant women of their HIV status. The aim of this study was to define the percentage of patients who received HIV tests between 2001 and 2007 in a German city hospital., Materials and Methods: In this retrospective cohort analysis at a University hospital in a German urban area, 12,873 deliveries were retrospectively analysed to determine whether an HIV test had been performed during prenatal counselling., Results: The number of HIV tests performed increased significantly between 2001 and 2007 from 59.6 to 76.7%. On average, 69.9% of the analysed deliveries were tested for HIV., Conclusions: Although awareness of the importance of HIV screening in newborns has increased in recent years, the numbers are still unsatisfactory. Therefore, further education is necessary to prevent HIV infection in early pregnancy and avoid HIV mother-to-child transmission.

Inhibins and activins are important regulators of the female reproductive system. Recently, a novel inhibin betaC subunit has been identified. However, only limited data on the expression of this novel inhibin-betaC subunit in normal and pathological human placentas exist. Tissue specimens of normal, preeclamptic, hemolysis, elevated liver enzymes, low platelets (HELLP), and intrauterine growth restriction (IUGR) pregnancies (n=24) were obtained at the conclusion of a cesarean section. Normal and pathological placental tissues were analyzed by an immunohistochemical staining reaction with a specific antibody against this novel inhibin-betaC subunit. Overall, expression of the inhibin-betaC subunit could be demonstrated in normal and pathological placental tissue. The immunoreactive score (IRS) for inhibin-betaC did not show any significant differences between normal, preeclamptic, HELLP, and IUGR tissue in extravillous trophoblast and syncytiotrophoblast cells. Immunolabelling of this novel inhibin-βC protein in normal and pathological placental tissue was demonstrated, although no differences in the staining intensity could be observed. Therefore, the inhibin-βC isoform might not primarily be involved in the pathogenesis of these pregnancy-associated disorders. The functional role of this novel inhibin-betaC subunit in normal and pathological human placenta is still quite unclear and should thus be further investigated.

Objective: Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease. Nearly 75% of all cases appear clinically unapparent and can cause, especially when getting chronically, infertility. Regarding pregnancy, a nationwide screening for C. trachomatis was established since April 1995. The aim of this study was to determine the percentage of tested patients throughout these 7 years to evaluate the execution of the German guidelines., Materials and Methods: Between 2001 and 2007, 12,865 patients were evaluated retrospectively concerning a Chlamydia trachomatis testing., Results: A test was performed for chlamydial infection in 10,088 patients (78.4%). 65 pregnant patients (0.5%) out of 1,008 tested patients were positive for Chlamydia trachomatis. The part of tested patients was rising significantly from 2001 to 2007. In 2001, 68.3% pregnant patients were tested. The number of screened patients increased continuously up to 85.2% in 2007 (p < 0.001). The percentage of positive tested patients ranged from 0.27% in 2003 to 0.74% in 2005 (mean 0.50%)., Conclusion: Since 1995, a screening for Chlamydia trachomatis has to be offered to every pregnant woman according to the German guidelines. The number of tested pregnant patients was rising from 68.3 to 85.2% within the evaluated 7 years, which would be a necessary and welcome trend. Interestingly, the mean prevalence of 0.5% of positive tested patients in this analysed urban population seems to be very low. An explanation might be the usage of the point-of-care (POC) tests and its low sensitivity. Testing by nucleic acid amplification might lead to a higher detection rate. Although the awareness concerning Chlamydia trachomatis testing during pregnancy seems to have been changed over the recent years, these data are still dissatisfactory.

Introduction: Worldwide, 20-30 million people are estimated to be infected with HTLV. HTLV-1 is endemic in Western Africa and Southern Japan, whereas HTLV-2 is considered to be spread among native American people., Materials and Methods: The impact of HTLV in gynaecology and obstetrics is being reviewed. Search strategy and selection criteria for identifying relevant data were performed by searching Medline, Current Contents, Web of Science, Embase and references from relevant articles. English and German gynaecological and infectious diseases textbooks as well as national and international guidelines and recommendations were also reviewed., Results: Transmission may occur by sexual intercourse or cellular blood products. Although materno-fetal transmission is debated, transmission through maternal breast milk has been confirmed. An HTLV-infection can lead to adult T-cell leukaemia (ATL) or cumulative opportunistic and neurological disorders that can occur with varying degrees of severity. Diagnosis can be done by antibody detection via the use of ELISA and western blot analysis as well as PCR diagnosis., Conclusion: Due to inadequate treatment options and the lack of an effective vaccination, prevention is currently only possible by restricting transmission, including the usage of condoms during sexual intercourse or avoiding breastfeeding in HTLV-seropositive mothers. If, due to socio-economic reasons, breastfeeding cannot be avoided, short-term breastfeeding for a maximum of up to 6 months is suggested.

Acinetobacter baumannii is a multidrug-resistant bacterium that is normally a commensal pathogen. This bacterium can lead to severe complications such as pneumonia, fever and septicaemia, because of limited treatment options. This case report describes a cervical A. baumannii infection during pregnancy and puerperium in a case of a patient treated in our hospital, because of insufficiency of cervix diagnosed in the 28 + 3 week of gestation. In spite of antibiotic treatment, the patient developed increasing contractions and chorioamnionitis, resulting in caesarean section in the 31st week of gestation. Moreover, although being treated with carbapenems, the patient presented postpartal with fever and septic symptoms, which could only be treated by escalation of the dosage of the given carbapenem. In conclusion, A. baumannii can lead to premature contractions and can be associated with chorioamnionitis during pregnancy. Moreover, it can also cause septic complications in the puerperium associated with long duration of hospitalisation. The management and therapy of this vaginal infection during pregnancy and puerperium is a real challenge to gynaecologists and obstetricians.

Introduction: Human chorionic gonadotropin is regarded as, at least, one of the main factors responsible for hyperemesis gravidarum by direct stimulation of the thyroid gland on the basis of a close homology to the structure of TSH. However, questions to this theory of hCG-induced gestational hyperthyroidism still remain., Case Report: We present for the first time a rare case of hyperemesis gravidarum in a patient with a previous removed thyroid gland and an adequate thyroxin replacement. In this case report we present an extended hyperemesis gravidarum in a patient after total thyroidectomy and thus artificially well-set thyroid parameters., Conclusion: Although transient hyperthyroidism is widely thought to be causative of a hyperemesis during pregnancy, this case report with a mildly hypothyroidism emphasizes that there might be other, yet unknown, factors that can cause such a severe complication.

Introduction: Nausea and vomiting during pregnancy (NVP) constitute a frequent and often highly unpleasant syndrome during the sensitive period of early pregnancy, which has been intensively investigated. However, many questions remain unanswered, particularly the counterintuitive association with a better pregnancy outcome. Under these circumstances our functional concept to interpret NVP as an evolutionary mechanism of complex adaptation to early pregnancy seems promising., Method: In this cross-cultural study data were collected from 565 mothers, who had given birth recently in South Africa, Guatemala and Germany, using a standardised questionnaire interview., Results: There was a cross-culturally similar prevalence and clinical presentation of NVP, showing a high degree of subjective suffering. We found evidence supporting a multifactoral aetiology of biological, psychological and sociological factors. Likewise, NVP seems to have multiple effects, concerning nutrition, behaviour, perception, psychology and social support., Discussion and Conclusion: Our new and previously existing data support the idea that NVP has been selected for by evolution, as a functional adaptation to vulnerable early pregnancy, which benefits mother and child. This assumption is supported by the correlation of NVP with a better foetal prognosis, the cross-culturally high prevalence and a favorable relation of low biological costs versus high effects. The benefit of NVP could be realised by nutritional change, increased social support, more passive and careful behaviour, earlier recognition of pregnancy and a positive influence on foetal development. To understand the functionality of NVP, one needs to consider the complex somato-psychoemotional interplay in the context of an environment of evolutionary adaptedness (EEA)., (Georg Thieme Verlag KG Stuttgart-New York.)

External cephalic version (ECV) at term is a safe procedure and reduces the incidence of cesarean sections for breech presentation. One of the known complications, however, is an ECV-related disruption of the placental barrier and a subsequent transfusion of fetal blood into maternal circulation. While the incidence of ECV-related fetomaternal hemorrhage (FMH) has been determined recently in a large trial using a manual Kleihauer-Betke test (KBT), questions remain on the amount of ECV-related FMH. KBT, which detects fetal red blood cells (RBC) on the basis of acidic resistance of fetal hemoglobin (HbF), is known to be a sensitive test, yet prone to procedural errors limiting its accuracy in quantifying FMH. In this study we investigated 50 patients for FMH before and after ECV, using a dual-color flow cytometric test kit with a lower limit of quantification of 0.05% fetal RBC in maternal peripheral blood. Three patients had a quantifiable increase of fetal RBC detected after ECV (0.06%; 0.08%; 0.1%). None of these subtle increments was predictable by ECV-related clinical parameters or translated into fetal compromise. Using a sensitive and accurate flow cytometric test method, our data provide further assurance to mothers on the safety of ECV at term.

Background: An elevated risk for unexplained stillbirth in subsequent pregnancies after cesarean section was reported in 2003. This finding would imply renewed discussions about stronger indications for cesarean sections., Objective: To find out whether there is an elevated risk for stillbirth in subsequent pregnancies after cesarean section in our cohort in Bavaria., Methods: As data linkage of records is not possible in Germany, we devised a suitable adjustment for bias correction. Second pregnancies in Bavaria/Germany after previous vaginal birth and previous cesarean section from 1987 to 2005 were analyzed. Risk of unexplained stillbirth was estimated by time-to-event analysis., Results: In our cohort of 629,815 second pregnancies, no elevated stillbirth risk in pregnancies after previous cesarean section compared to previous vaginal birth was noted (crude risk 0.22% in both groups; hazard ratio (HR) 1.00; P = 1.0). A slightly decreased risk for stillbirth after previous cesarean section for the period of 1994-2005 (HR 0.674; P = 0.04) could be shown., Conclusion: We found no elevated stillbirth risk in pregnancies after previous cesarean section. The significantly lower risk for stillbirths after previous cesarean section in the period 1994-2005 is interpreted as consequence of improved obstetric surveillance. With our adjustment for bias correction, we hope to have found a way to make our data largely comparable with other sources reported in the literature. However, because of the strict German data protection act, the Bavarian birth register is only of limited use for the presented study.

Introduction: Peripartum hemorrhage is one of the leading causes of maternal death worldwide (25%)., Methods: Selective literature review, including international guidelines, for assessment of the causes and optimal management of this condition., Results: The major causes of hemorrhage are uterine atony, placenta previa, and abruptio placentae. The diagnosis of hemorrhage is suspected from its clinical manifestations and confirmed by ultrasonography. In placenta previa, the placenta is implanted in the lower uterine segment and may cover the internal cervical os. Placenta previa is more common in older and multiparous mothers, as well as in mothers who have previously undergone a cesarean section. Placental abruption is defined as separation of the placenta from the uterine wall before delivery of the infant. The risk factors for this condition include preeclampsia, advanced maternal age, and trauma. When it presents with manifestations of acute blood loss, premature abruption placentae must be diagnosed rapidly and treated without delay to save the life of the mother and child. A rare, but highly lethal, cause of bleeding is amniotic fluid embolism, which manifests itself with sudden and unexplained peripartum respiratory distress and cardiovascular collapse. Amniotic fluid embolism is associated with high fetal and maternal mortality (20% and 60% to 80%, respectively) even when it is optimally treated., Discussion: Peripartum hemorrhage is an important source of maternal and fetal morbidity and mortality. The prognosis for both mother and child can be markedly improved if the risk factors for hemorrhage are recognized and the problem is treated rapidly and appropriately when it arises.

Pulmonary embolism in pregnancy is difficult to diagnose because of the technical limitations. We report on a diagnosis of severe pulmonary embolism during pregnancy using the serum parameter NT-proBNP as a marker for right ventricular dysfunction following pulmonary embolism.

Severe peripartum hemorrhage (PPH) contributes to maternal morbidity and mortality and is one of the most frequent emergencies in obstetrics, occurring at a prevalence of 0.5-5.0%. Detection of antepartum risk factors is essential in order to implement preventive measures. Proper training of obstetric staff and publication of recommendations and guidelines can effectively reduce the frequency of PPH and its resulting morbidity and mortality. Therefore, an interdisciplinary expert committee was formed, with members from Germany, Austria, and Switzerland, to summarize recent scientific findings. An up-to-date presentation of the importance of embolization and of the diagnosis of coagulopathy in PPH is provided. Furthermore, the committee recommends changes in the management of PPH including new surgical options and the off-label use of recombinant factor VIIa.

Alterations of the metabolic and hormonal environment of the fetus may cause predispositions to the development of disorders and diseases in later life. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes. Elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism. Diagnosis and therapy of gestational diabetes in time may prevent metabolic and cardiovascular diseases in later life. This concept has new important implications for chances and challenges of perinatal preventive medicine in the future.