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The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.Zusammenfassung Die Schwangerschaftscholestase (Intrahepatic Cholestasis of Pregnancy, ICP) ist die haufigste schwangerschaftsspezifische Lebererkrankung. Das Leitsymptom Juckreiz und eine begleitende Konzentrationserhohung von Gallensauren im Serum und/oder der Alanin-Aminotransferase (ALT) sind richtungsweisend fur die Diagnosestellung. Insgesamt ist die mutterliche Prognose gut. Das fetale Outcome ist abhangig von der Gallensaurenkonzentration. Die ICP ist sowohl mit einer Fruhgeburt als auch mit dem intrauterinem Fruchttod (IUFT) assoziiert. Ursachlich ist eine akute fetale Asphyxie und nicht eine chronische uteroplazentare Dysfunktion. Daher ist ein pradiktives Monitoring, z.B. durch CTG oder Ultraschall nicht moglich. Eine medikamentose Therapie mit Ursodeoxycholsaure (UDCA) bessert den Juckreiz - beeinflusst jedoch das fetale Outcome nicht nachweislich. Eine Entbindungsindikation ergibt sich in Abhangigkeit der Gallensaurenkonzentration und des Gestationsalters. In Folgeschwangerschaften besteht ein hohes Wiederholungsrisiko.

Bei ca. 3 % der Schwangerschaften kommt es zu einem frühen vorzeitigen Blasensprung („preterm premature rupture of the membranes“, PPROM). Da bei PPROM mit hoher Wahrscheinlichkeit mit einer MIAC („microbial invasion of the amniotic cavity“) – bereits vorbestehend oder sekundär nach Blasensprung – zu rechnen ist, ist auch die Wahrscheinlichkeit für eine intraamniale Inflammation (IAI) signifikant erhöht. Eine IAI ist mit kurzer Latenz bis zur Geburt des Kindes und mit ungünstigen Verläufen mit kurz- und langfristig erhöhter Morbidität des Neugeborenen assoziiert, besonders bei Entwicklung eines FIRS („fetal inflammatory response syndrome“). Die Vorhersage einer IAI anhand mütterlicher Parameter ist nur schwer möglich. Die neu eingeführte Definition Triple I („infection, inflammation, or both“) fokussiert auf den Parameter maternale Körpertemperatur, der bei gesichertem Anstieg auf ≥ 38,0 °C und fehlendem Anhalt für eine andere Fieberursache sowie durch mindestens einen weiteren Parameter (fetale Tachykardie > 160 bpm („beats per minute“) für mindestens 10 min, maternale Leukozyten > 15.000/µl ohne Gabe von Kortikosteroiden, purulenter Fluor aus dem Muttermund) bestätigt werden soll. Die Bestätigung der Diagnose Triple I ist zuverlässig nur durch eine Plazentahistologie („histologically confirmed chorioamnionitis“, HCA) möglich. Eine Bestätigung durch Amniozentese (positive Gram-Färbung, Glukosekonzentration 30 Zellen/mm3, positive Bakterienkultur) dauert zu lange und ist unzuverlässig. Auch serielle CRP(C-reaktives Protein)-Bestimmungen ermöglichen keine zuverlässige Diagnose einer IAI. Studien zur Bestimmung von IL(Interleukin)-6 aus dem Zervikalkanal und dem hinteren Scheidengewölbe sind vielversprechende Verfahren, deren Validierung abgewartet werden muss.

Introduction E-cigarette use during pregnancy is a risk factor for maternal and fetal health. Early studies on animals showed that in utero exposure to e-cigarettes can have negative health outcomes for the fetus. There has been only limited research into the risk perceptions of e-cigarette use during pregnancy. This study was conducted to comprehensively characterize the constructs of risk perceptions with regard to e-cigarette use during pregnancy using an Integrated Health Belief Model (IHBM). Methods Our STudy on E-cigarettes and Pregnancy (STEP) used a mixed methods approach, with the study divided into an initial qualitative part and a quantitative part. A netnographic approach was used for the first part, which consisted of the analysis of 1552 posts from 25 German-language online discussion threads on e-cigarette use during pregnancy. Using these qualitative results, a quantitative questionnaire was developed to explore risk perception constructs about e-cigarette use during pregnancy. This questionnaire was subsequently administered to pregnant women (n = 575) in one hospital in Hamburg, Germany. Descriptive and bivariate analysis was used to examine differences in risk perception according to participantsʼ tobacco and e-cigarette user status before and during pregnancy. While the study design, methods and sample have been extensively described in our recently published study protocol in the January 2020 issue of Geburtshilfe und Frauenheilkunde, this paper is devoted to a presentation of the results of our mixed methods study. Results Themes related to perceived threats identified in the qualitative study part were nicotine-related health risks and potential health risks of additional ingredients. Perceived benefits were possibility and facilitation of smoking cessation and a presumed potential to reduce harm. The subsequent quantitative part showed that nearly all participants (99.3%) perceived e-cigarettes which contained nicotine as constituting a threat to the health of the unborn child. The most commonly perceived barrier was health-related (96.6%), while the most commonly perceived benefit was a reduction in the amount of tobacco cigarettes consumed (31.8%). We found that particularly perceived benefits varied depending on the participantʼs tobacco and e-cigarette user status. Conclusion When considering future prevention strategies, the potential health risks and disputed effectiveness of e-cigarettes as a tool for smoking cessation need to be taken into account and critically discussed.

Background The rate of preterm births in Germany is 8.6%, which is very high compared to other European countries. As preterm birth contributes significantly to perinatal morbidity and mortality rates, the existing prevention strategies need to be optimized and expanded further. About ⅔ of all women with preterm birth have preterm labor or premature rupture of membranes. They are bracketed together under the term “spontaneous preterm birth” as opposed to iatrogenic preterm birth, for example as a consequence of preeclampsia or fetal growth retardation. Recent studies suggest that low-dose aspirin does not just reduce the rate of iatrogenic preterm births but can also further reduce the rate of spontaneous preterm births. This review article presents the current state of knowledge. Method A selective literature search up until April 2020 was done in PubMed, using the terms “randomized trial”, “randomized study”, “spontaneous preterm birth”, and “aspirin”. Results Secondary analyses of prospective randomized studies on the prevention of preeclampsia with low-dose aspirin show that this intervention also significantly reduced the rate of spontaneous preterm births in both high-risk and low-risk patient populations. The results of the ASPIRIN trial, a prospective, randomized, double-blinded multicenter study carried out in six developing countries, also point in this direction, with the figures showing that the daily administration of 81 mg aspirin starting before 14 weeks of gestation lowered the preterm birth rate of nulliparous women without prior medical conditions by around 11% (11.6 vs. 13.1%; RR 0.89; 95% CI: 0.81 – 0.98, p = 0.012). Conclusion Further studies on this issue are urgently needed. If these confirm the currently available results, then it would be worth discussing whether general aspirin prophylaxis for all pregnant women starting at the latest in 12 weeks of gestation is indicated.

Objectives Active and passive exposure to tobacco cigarettes during pregnancy is associated with multiple negative health outcomes for the fetus. In addition, exposure to e-cigarettes has been progressively discussed as a new threat to fetal health. Until now, there has been a lack of studies examining active and passive exposure to tobacco and e-cigarettes among pregnant women. The objective of our current STudy on E-cigarettes and Pregnancy (STEP) was to advance and complement the current knowledge regarding active and passive exposure to tobacco and e-cigarettes before pregnancy and during early and late pregnancy. Methods One element of the STEP study was a quantitative cross-sectional design: A sample of 540 pregnant women recruited at an obstetrician clinic in Hamburg from April 2018 to January 2019 were surveyed once via a standardized questionnaire and provided complete information regarding their consumption of tobacco and e-cigarettes. We performed a descriptive analysis of tobacco and e-cigarette use before pregnancy and during early and late pregnancy, as well as bivariate analysis of these variables with sociodemographic determinants. Passive exposure was assessed by asking the participating pregnant women about the consumption of tobacco and e-cigarettes by their partners, in general, and in their homes. Results Before pregnancy, 20.0% of the participants used tobacco cigarettes exclusively, 1.3% used e-cigarettes exclusively, and 6.5% were dual users. Educational level was significantly associated with tobacco cigarette use (p Conclusions for Practice Among pregnant women, the use of tobacco cigarettes remains prominent before and during pregnancy, while e-cigarette use predominately occurs before pregnancy. Our study shows that pregnant women are frequently exposed to their partners’ tobacco and e-cigarette use within their homes. Strategies to reduce such exposure should be further intensified.

Introduction During pregnancy, the motherʼs healthy lifestyle is crucial for the health of the fetus. Potential risk factors for maternal and child health should therefore be identified and reduced as early as possible. The consumption of e-cigarettes represents one of these potential risk factors. Exploring risk perceptions about e-cigarette use during pregnancy can provide early indications of possible user motives. Therefore, our mixed methods STudy on E-cigarettes and Pregnancy (STEP) aimed to comprehensively analyze risk perceptions about e-cigarette use during pregnancy based on an Integrated Health Belief Model (IHBM). This paper describes the study design, methods, sample population and limitations of STEP. Methods Our sequential mixed methods study combined qualitative and quantitative approaches. In the qualitative section of the study which preceded the quantitative part of the study, we aimed to characterize risk perceptions about e-cigarette use during pregnancy. We used a netnographic research approach which analyzed discussion threads in online forums dealing with e-cigarette use during pregnancy. The analysis was based on an IHBM. Identified themes were incorporated in the questionnaire which was developed for the quantitative part of the study. The quantitative section aimed to quantify, among other things, perceived threats, barriers and benefits and to explore differences in risk perception according to sociodemographic characteristics and tobacco and e-cigarette usage. Results In the qualitative section, 1552 posts in 25 online discussion threads dealing, inter alia, with e-cigarette use during pregnancy were identified. The quantitative part looked at the responses in the questionnaires handed in by 575 pregnant women who attended a hospital in Hamburg (Germany) from April 2018 to January 2019 (response rate: 27.5%). Conclusion Data collection was successful for both the qualitative and quantitative parts of the study. When interpreting the results of STEP, different limitations should be taken into account. The results of STEP provide starting points for the development of tailored preventive measures for pregnant women.

Current international guidelines recommend tocolytic treatment by at least 48 h to complete fetal lung maturation and to ensure in-utero transfer to a perinatal center before 34 weeks of gestation in patients with threatened preterm birth. According to the results of former surveys, significant differences between daily clinical practice patterns and evidence-based guideline recommendations regarding tocolytic treatment have been demonstrated. We compared data from a nation-wide survey on the practice of initial tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth".632 obstetric units in Germany received a link to an online questionnaire between January 20th and March 31st 2020, which was developed according to national and international recommendations and guidelines. Collected data was descriptively analyzed by performing measures of frequency.The response rate was 19%; 51 (42.5%) of the respondents consider CTG tracing with ≥ 4 contractions within 20 min, 49 (40.8%) cervical length measurement of ≤ 25 mm and 13 (10.9%) subjective contractions as the most significant decision-making criteria for tocolysis; 47 (39.2%) of obstetric units initiate tocolysis earliest at 23 + 0, 34 (28.3%) at 22 + 0, 26 (21.7%) at 23 + 5 and 13 (10.8%) at 24 + 0 weeks of gestation; 104 (86.7%) stop tocolysis latest at the 34 + 0 weeks of gestation, 42 (35.0%) obstetric units administer antenatal corticosteroids at 23 + 5, 16 (13.3%) at 22 + 0, and 13 (10.8%) at 24 + 0 weeks of gestation. Calcium channel blockers are the first-line tocolytic drug used by 59 (49.1%) of the obstetric units, followed by intravenous betamimetics as bolus (n = 26, 21.7%) and atosiban (n = 20, 16.7%). Severe side-effects were observed by 105 (70%) of the respondents in association with the use of betamimetics, 14 (9.3%) with the use of nifedipine and 30 (20.0%) with nitroglycerine patches. The German guideline was considered the most important decision-making support by 78 (65%) of the obstetric units, followed by hospital specific SOPs/algorithms (n = 31, 25.8%).Our survey highlights a considerable discrepancy between evidence-based guideline recommendations and daily clinical practice.

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 position paper describes clinically important, practical aspects of cervical pessary treatment. Transvaginal ultrasound is standard for the assessment of cervical length and selection of patients who may benefit from pessary treatment. Similar to other treatment modalities, the clinical use and placement of pessaries requires regular training. This training is essential for proper pessary placement in patients in emergency situations to prevent preterm delivery and optimize neonatal outcomes. Consequently, pessaries should only be applied by healthcare professionals who are not only familiar with the clinical implications of preterm birth as a syndrome but are also trained in the practical application of the devices. The following statements on the clinical use of pessary application and its removal serve as an addendum to the recently published German S2-consensus guideline on the prevention and treatment of preterm birth.Dieses Positionspapier beschreibt klinisch wichtige praktische Aspekte der Zervixpessartherapie. Zur Beurteilung der Zervixlänge und um Patientinnen auszuwählen, die von einer Pessartherapie profitieren könnten, wird standardmäßig transvaginaler Ultraschall eingesetzt. Wie bei anderen Behandlungsmodalitäten auch, ist es wichtig, regelmäßig Schulungen zum klinischen Einsatz und zur Pessarplatzierung durchzuführen. Diese Schulungen sind unerlässlich, um eine korrekte Platzierung von Pessaren im Notfall zu gewährleisten, Frühgeburten zu verhindern und die neonatale Ausgangssituation zu optimieren. Pessare sollten nur von medizinischen Fachleuten eingesetzt werden, die nicht nur mit den klinischen Implikationen einer Frühgeburt als Syndrom vertraut sind, sondern auch in der praktischen Anwendung von Pessaren geschult sind. Die folgenden Aussagen zum klinischen Einsatz von Pessaren und deren Entfernung dienen als Ergänzung der vor Kurzem veröffentlichten deutschen S2-Richtlinie zur Prävention und Therapie der Frühgeburt.

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.

The administration of a single course of corticosteroids before week 34 + 0 of gestation in cases with impending preterm birth is now standard procedure in obstetric care and firmly established in the guidelines of different countries. But despite the apparently convincing data, numerous aspects of this intervention have not yet been properly studied. It is still not clear which corticosteroid achieves the best results. There are very few studies on what constitutes an appropriate dose, circadian rhythms, the time frame in which corticosteroids are effective, and the balance between the risks and benefits of repeat administration. As the existing studies have rarely included patients before week 24 + 0 of gestation, we have very little information on the possible benefits of administering corticosteroids before this timepoint. If corticosteroids are administered antenatally after week 34 + 0 of gestation, the short-term benefit may be offset by the long-term adverse effect on psychomotor development. This present study summarizes the current state of knowledge regarding these issues.

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

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

β2-sympathomimetics are used in obstetrics as tocolytic agents, despite a remarkable profile of side effects. Recently, the β2-sympathomimetic tocolytic drug hexoprenaline was identified as an independent risk factor for the development of infantile hemangioma (IH) in preterm infants. The aim of this study was to evaluate whether this observed effect was applicable to other β2-mimetic tocolytic agents like fenoterol. Clinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups. N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619–1.384) or in a subgroup of neonates

Preterm birth is one of the major global health problems and part of the Millennium Development goals because of the associated high number of perinatal or neonatal mortality and long-term risks of neurodevelopmental and metabolic diseases. Transvaginal sonography has meanwhile been established as a screening tool for spontaneous preterm birth despite its relatively low sensitivity when considering only the cervical length. Vaginal progesterone has been shown to reduce prematurity rates below 34 weeks in a screening population of singleton pregnancies. Up to now, no positive long-term effect could be demonstrated after 2 years. It seems to have no benefit to prolong pregnancies after a period of preterm contractions and in risk patients without cervical shortening. Meta-analyses still demonstrate conflicting results dependent on quality criteria used for selection. A cerclage is only indicated in singleton pregnancies with previous spontaneous preterm birth and a combined cervical shortening in the current pregnancy. Nevertheless, the short- and long-term outcome has never been evaluated, whereas maternal complications may be increased. There is no evidence for a prophylactic cervical cerclage in twin pregnancies even in cases with cervical shortening. Emergency cerclage remains an indication after individual counseling. The effect of a cervical pessary in singleton pregnancy seems to be more pronounced in studies where a few investigators with increasing experience have treated and followed the patients at risk for preterm birth. Mainly in twin pregnancies, pessary treatment seems to be promising compared to other treatment options of secondary prevention when the therapy is started at early stages of precocious cervical ripening. At present, several international trials with the goal to reduce global rates of prematurity are in progress which will hopefully allow to specify the indications and methods of intervention for certain subgroups. When trials are summarized, prospective meta-analyses carry a lower risk of bias than the meanwhile uncontrolled magnitude of retrospective meta-analyses with conflicting results. Frühgeburten gehören zu den wichtigsten Gesundheitsproblemen weltweit und gehören wegen der damit verbundenen hohen perinatalen und neonatalen Mortalitätsraten und der Langzeitrisiken für neurologische Entwicklungsstörungen und Stoffwechselkrankheiten zu den Millenniums-Entwicklungszielen. Obwohl die Sensitivität der transvaginalen Sonografie bei der Messung der zervikalen Länge relativ niedrig ist, hat sich diese Methode als Screeninginstrument bei der Prävention von spontanen Frühgeburten etabliert. Die vaginale Verabreichung von Progesteron hat in einer Population werdender Mütter mit Einlingsschwangerschaft die Frühgeburtsraten vor der 34. Woche nachweislich verringert. Bislang wurden aber keine positiven Langzeitwirkungen nach 2 Jahren nachgewiesen. Es scheint, dass die Herauszögerung der Schwangerschaft nach einiger Zeit mit vorzeitigen Wehen sowie bei Risikopatientinnen ohne Zervixverkürzung keine Vorteile bietet. Die Ergebnisse von Metaanalysen sind nach wie vor widersprüchlich und hängen von den gewählten Qualitätskriterien ab. Eine Cerclage ist nur bei Einlingsschwangerschaften nach spontaner Frühgeburt in einer vorherigen Schwangerschaft verbunden mit einer Zervixverkürzung in der aktuellen Schwangerschaft indiziert. Die kurz- und langfristigen Auswirkungen wurden nicht untersucht, obwohl sie möglicherweise zu einer Erhöhung der mütterlichen Komplikationen führen könnten. Es gibt keine Hinweise, dass die prophylaktische zervikale Cerclage vorteilhaft ist bei Zwillingsschwangerschaften, selbst bei Frauen mit Zervixverkürzung. Je nach individueller Beratung mag eine Not-Cerclage indiziert sein. Die Wirkung eines zervikalen Pessars in Einlingsschwangerschaften war ausgeprägter in Studien, bei denen die Untersucher zunehmende Erfahrung hatten bei der Behandlung und Nachbetreuung von Frauen mit einem höheren Risiko für Frühgeburtlichkeit. Im Vergleich zu anderen Optionen für die Sekundärprävention scheint die Behandlung mit einem Pessar erfolgversprechend, vor allem bei Zwillingsschwangerschaften, wenn früh mit der Behandlung begonnen wird, d. h. in den ersten Stadien einer vorzeitigen Zervixreifung. Zurzeit laufen mehrere internationale Studien, die alle das Ziel haben, die Frühgeburtsraten weltweit zu reduzieren, und die hoffentlich weitere Hinweise auf die Indikationen und Interventionsmethoden für bestimmte Untergruppen liefern werden. Bei der Zusammenfassung von Studien wiesen prospektive Metaanalysen ein niedrigeres Verzerrungsrisiko auf als die inzwischen unkontrollierte Menge retrospektiver Metaanalysen mit ihren widersprüchlichen Ergebnissen.

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.

BACKGROUND: The preterm birth rate in Germany has remained unchanged at 8–9% since 2009. Preterm birth is the most common cause of neonatal morbidity and mortality. In the absence of a causal treatment, it is important to lower the risk of preterm birth by preventive measures in prenatal outpatient care. METHODS: This review is based on pertinent publications from the years 2000–2019 that were retrieved by a selective search in PubMed. RESULTS: The clinical risk factors for preterm birth—known mainly from retrospective cohort studies—include previous preterm birth (adjusted odds ratio [aOR]: 3.6), multiple pregnancy (relative risk [RR]: 7.7), nicotine consumption (aOR: 1.7), and a short uterine cervix, i.e.

With the approval of CD19-targeted chimeric antigen receptor (CAR) T cells for the treatment of B cell malignancies, clinicians have gained valuable insights into the power and challenges of cellular therapies. In this issue of the JCI, Maluski et al. showed that a CAR containing a CD28 costimulatory domain drives progeny differentiation to resemble that of NK cells, which have the potential for an off-the-shelf cell therapy. These CAR-induced killer (CARiK) cells displayed potent antitumor function and killed across the MHC barrier in vivo. After performing in vitro and in vivo mouse studies, the authors also successfully differentiated human umbilical cord blood-derived progenitor cells into CARiK cells. These unique cells may address some of the current challenges associated with first-generation CARs, such as prolonged production that requires patients to wait weeks for infusion. We believe this innovative progenitor gene-engineered lymphoid system has the potential for clinical translation.

This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups.Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus).Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.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.

This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recently published scientific literature, the experience of the members of the guideline commission and the views of self-help groups.The members of the participating medical societies and organizations developed Recommendations and Statements based on the international literature. The Recommendations and Statements were adopted following a formal consensus process (structured consensus conference with neutral moderation, voting done in writing using the Delphi method to achieve consensus).Part 2 of this short version of the guideline presents Statements and Recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.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.

Objective: In March 2012, a universal screening for gestational diabetes mellitus (GDM) was implemented in Germany. Despite international recommendations, a two-step approach was introduced [step 1: 50-g glucose challenge test (GCT); if GCT is suspicious, step 2 follows: 75-g oral glucose tolerance test with (OGTT)]. This qualitative study aimed at examining how gynecologists administer the screening for GDM in daily practice, whether they perceive any difficulties, and whether they have suggestions for improvement.Material and Methods: Seventeen resident gynecologists were interviewed face-to-face in semi-structured interviews. The interviews were recorded, transcribed verbatim, coded, and analyzed using qualitative content techniques.Results: We revealed differences in the screening administration. Three gynecologists directly offered the second step of the two-step screening (OGTT) instead of completing the first step before offering the second step. These gynecologists only conducted GCT if the woman (with statutory health insurance) was not willing to pay for OGTT. Critique concerns the late introduction of billing codes, lack of information from official institutions, unavailability of readymade syrup with 50-g glucose, and lack of information material for pregnant women.Conclusion: Our results reflect that not all gynecologists appear to conduct the screening conforming to the maternity directive. However, this has to be validated in larger quantitative surveys. That some gynecologists directly conducted OGTT may fuel the discussion regarding the screening procedure. The two-step approach was already highly controversial at the time of introducing the screening because national and international organizations recommend a one-step approach. Therefore, our results are also relevant for other countries who have implemented a two-step screening and for countries planning to implement a screening.

βClinical prospectively collected data of all infants born between 2001 and 2012 and admitted to the neonatal intensive care unit (NICU) at Heidelberg University Hospital and respective maternal data were merged. For the current retrospective cohort study, cases (IH) were matched to controls (no IH) at a ratio of 1:4, adjusting for birth weight, gestational age, gender and multiple gestations. Prenatal exposure to fenoterol and perinatal outcome were analyzed in the total cohort and in subgroups.N = 5070 infants were admitted to our neonatal department, out of which n = 172 infants with IH were identified and compared to n = 596 matched controls. Exposure to fenoterol was not associated with a higher rate of IH in the total matched population (OR 0.926, 95% CI 0.619-1.384) or in a subgroup of neonates 32 weeks of gestation or with a birth weight 1500 g (OR 1.127, 95% CI 0.709-1.791). In the total matched population, prenatal exposure to glucocorticoids was associated with a reduced occurrence of IH (OR 0.566, 95% CI 0.332-0.964) and neonates with IH showed a prolonged total hospital stay compared to controls (69 vs. 57 days, p = 0.0033). Known risk factors for IH were confirmed by our large study cohort and included female gender, low birth weight, preterm birth and multiple gestations (all p 0.005).Exposure to fenoterol during pregnancy does not increase the occurrence of IH. Further studies are needed to explore differences in the risk profiles of different β

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

Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis.

PURPOSE: Depression and anxiety disorders are the most common mental disorders and are widespread in our society. A considerable number of women suffer from these mental disorders either prior to, during or after pregnancy. They can cause severe complications during and after pregnancy. However, the prevalence and clinical presentation of depression and anxiety disorders during pregnancy have received little attention. In this article we review the medical literature as it relates to the prevalence and clinical presentation of depression and anxiety disorders during pregnancy. The aim of this study is to investigate the growing body of literature on maternal depression and anxiety during pregnancy. Its purpose is to present an overview of antenatal depression and anxiety and the clinical issues and implications involved. To develop a better understanding we describe the typical symptoms of these disorders and discuss the side effects on pregnant women and the developing fetus afterwards. The treatment options in clinical practice are explained, and the Edinburgh Postnatal Depression Scale (EPDS), which can be used as a simple screening instrument, is shown. MATERIAL AND METHODS: A search for empirical articles indexed in electronic databases (Medline, Pubmed) was conducted using combinations of the following search terms: pregnancy, childbirth, depression, postpartum, panic disorder, anxiety disorder, low birthweight, growth retardation, preterm birth or treatment. We included 59 articles published between 1986 and 2009. RESULTS: A high level of depressive or anxiety symptoms during pregnancy were found in combination with fetal intrauterine growth retardation or preterm birth. A few studies were able to demonstrate an association. The pathomechanism remains partly unclear. Most likely those symptoms cause a change in the signalling pathway of cortisol, which has been demonstrated in animal research. It is not easy to establish a diagnosis during pregnancy. To differentiate between reactive symptoms and real psychopathology a psychiatrist or psychotherapist would often need to be involved. Treatment options range from supportive psychotherapy to treatment with antipsychotic drugs in severe cases. CONCLUSION: Depressive and anxiety disorders are the most common mental disorders in women during their reproductive years. The appearance of these disorders is heterogeneous. Making a diagnosis and treatment of the disorder is difficult during pregnancy. Given the growing evidence that depression, stress, anxiety and psychotropic medications all involve fetal exposure, pregnant women with depression or anxiety and their gynecologists face significant treatment dilemmas. Both treating and not treating the disorder can have negative side effects. Early detection of depression and anxiety disorders, confirmation of the diagnosis and early initiation of treatment options could limit prenatal complications and prevent their postpartum exacerbation.

Objective The significant role of direct contact between hematopoietic progenitor cells (HPC) and the cellular microenvironment for maintaining "stemness" has been demonstrated. Human mesenchymal stem cell (MSC) feeder layers represent a surrogate model for this interaction. Specific adhesion molecules are responsible for this cell−cell contact. Methods To define cell−cell contact between HPC and MSC, we have studied adhesive interaction of various fractions of HPC by using a novel assay based on gravitational force upon inversion. Adherent and nonadherent cells were separated and further analyzed with regard to gene expression and long-term hematopoietic culture initiating cell (LTC-IC) frequency. Results HPC subsets with higher self-renewing capacity demonstrated significantly higher adherence to human MSC (CD34 + vs CD34 − , CD34 + /CD38 − vs CD34 + /CD38 + , slow dividing fraction vs fast dividing fraction). LTC-IC frequency was significantly higher in the adherent fraction than in the nonadherent fraction. Furthermore, genes coding for adhesion proteins and extracellular matrix were higher expressed in the adherent subsets of CD34 + cells (fibronectin 1, cadherin 11, vascular cell adhesion molecule-1, connexin 43, integrin β-like 1, and TGFBI). Conclusion In this study we have demonstrated that primitive subsets of HPC have higher affinity to human MSC. The essential role of specific junction proteins for stabilization of cell−cell contact is indicated by their significant higher expression.

Objective: Pregnancies of women with glucose tolerance disorders are still associated with high maternal and perinatal morbidity. In the present population-based study we investigated the maternal risks and complications in pregnancies of women with preconceptional and gestational diabetes compared with pregnancies of non-diabetic women. Methods: The data of 913255 pregnancies between 1987 and 1999 documented by the Perinatal Registry of Lower Saxony, Germany, were evaluated in a retrospective population-based study. The obstetric parameters of 3439 women with preconceptional diabetes mellitus (PDM), 4051 women with gestational diabetes mellitus (GDM) and 905765 non-diabetic women (NDM) were analyzed and a trend analysis was carried out. Results: The pregnancies of diabetic women showed a significantly higher rate of hypertension (PDM vs. NDM odds ratio [OR] 3.083; GDM vs. NDM OR 3.832; p

Purpose: Cervical dilatation during parturition is associated with a significant increase of interleukin (IL)-6 and IL-8. The purpose of this study was to localize the respective messenger RNA and to quantitate their protein levels during various stages of dilatation. Methods: Protein extracts from 34 biopsy specimens of the lower uterine segment at various stages of cervical dilatation ( 6 cm) were subjected to enzyme linked immunosorbent assay for IL-6 and IL-8 to document their concentration. The respective mRNA expression was studied using reverse transcriptase PCR using IL-6 and IL-8 specific primers. Localization of IL-6 and IL-8 was done by in situ hybridization using biotinylated probes. Results: The IL-6 and IL-8 concentrations increased significantly in the lower uterine segment tissues at 4–6 cm of dilatation. Expression of IL-8 was seen in all the tissues at or more than 4 cm dilatation, whereas IL-6 expression was inconsistent. In situ hybridization localized IL-6 and IL-8 mRNA to the glandular epithelium. Conclusions: The increase in the inflammatory cytokines (IL-6 and IL-8) during parturition is associated with cervical effacement.

Vorgestellt wird der klinische Fall einer 28jahrigen Patientin, I Gravida, die aufgrund der Verdachtsdiagnose Hydrocephalus in die Universitats–Frauenklinik uberwiesen wurde. Sonographisch zeigte sich das Bild eines ausgepragten Aneurysma der Vena galeni in der 21+5. SSW. Zunachst wurden weitere diagnostische Schritte durchgefuhrt: Karyotypisierung, Fetal-MRT und sonographische Verlaufskontrollen. Im weiteren Verlauf kam es dann trotz einer Digitalisierung als therapeutischen Versuch der Behandlung der Herzinsuffizenz zu einer Progredienz der cardialen Situation und schlieslich bei drastischer Verschlechterung zu einem IUFT in der 31. SSW. Neben dem intrauterinen Verlauf gibt der case report eine Ubersicht uber die seltene Fehlbildung der V. galeni Malformation, deren Management und postoperative Behandlungsmoglichkeiten.

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.

First trimester risk assessment for fetal aneuploidies is computed on the base of a general background risk, which is depending on the maternal age. Thereby, the adjusted risk tends to rise with increasing age. Obversely, more unsuspicious fetal parameters [measurement of the nuchal translucency (NT) and biochemical parameters, free beta human chorionic gonadotropine (fbetaB-Hcg) and pregnancy associated plasma protein A (Papp-A)] have to be observed to result in an unsuspicious test at higher age. It was the aim of this study to investigate the potential value of a novel risk assessment algorithm explicitly disregarding the maternal age.This was an ultrasound cohort study of 1,463 singleton pregnancies at 11-14 weeks of gestation undergoing a first trimester screening for fetal aneuploidies by measuring the (NT), Papp-A and fbeta-hCG. In each case, the pregnancy outcome was obtained. Regarding either the detection of genetic affections or the combined detection of genetic or somatic anomalies, the test performance parameters (sensitivity, specificity, positive and negative predictive values) were calculated and compared with each other. For risk calculation the standard Fetal Medicine Foundation (FMF)-Software and an alternative software with a similar algorithm (JOY-Software) were utilized. Compared to this, the risk assessment had been modified by implementing a novel calculation algorithm (advanced first trimester screening algorithm, AFS) purposely disregarding the maternal age and again, the test performance parameters had been computed and were compared with the first ones.At the mere genetic analysis, all four test-strategies revealed to have identical sensitivity and negative predictive values. Compared to the standard FMF-Software, the JOY-Software showed a reduced false positive rate. In addition, in both softwares, the false positive rate is highly significant-reduced by implementing the AFS-algorithm. At combined genetic and somatic analysis, analogous results on different counts could be found.In the effort to create an algorithm characterising somatic and fetal conditions of the fetus most properly, the inclusion of maternal age is not a helpful value and excluding the age from risk calculation leads to a high significant reduction of the false positive rate. Further, a comparable marked increase of both, specificity and positive predictive values, can be achieved for the FMF- and JOY-Software on the background of the generally more favourable JOY test performance.