The impact of gender on the self-confidence of practical and surgical skills among OBGYN residents: a trinational survey.

INTRODUCTION: Gender disparities exist in the OBGYN discipline. This study investigates, for the first time, whether gender impacts on the confidence of practical and surgical skills among OBGYN residents, and of being prepared to work as a specialist. METHODS: The gynecological societies of Austria, Germany, and Switzerland established a web-based survey of 30 questions that was sent to all registered OBGYN members-in-training from August to September 2020. Data collection, controlling and analysis were performed by the Swiss Federal Institute of Technology in Zurich (ETH). RESULTS: A total of 422 participants took part in the survey, of which 375 (88.9%) were female, 46 (10.9%) were male, and one (0.2%) was divers. The diverse participant was excluded from further analyses. The gender distribution was comparable in all three countries. Multiple regression analyses showed that gender is an independent variable significantly impacting on the confidence levels in performing standard gynaecological (p = 0.03) and obstetric (p < 0.001) procedures. Similarly, the feeling of confidence in being prepared for working as a specialist in a clinic showed to be gender-dependent (p < 0.001), however, not the feeling of being prepared for working as specialist in an outpatient setting (p = 0.37). The "female factor" significantly decreases the confidence rating for surgical and practical skills and for working in a hospital. Covariates including year of training, country, workload, receiving regular feedback, and implemented simulation training were included in all analyses. DISCUSSION: Improvements of residency programs to promote female doctors to overcome factors reducing their confidence in their own OBGYN skills are highly warranted.

Operating during pregnancy: A needs assessment among surgical residents in Austria.

In Austria, female physicians must immediately disrupt their surgical training as soon as their pregnancy is announced. In Germany, surveys on the topic of "female surgeons performing surgery during pregnancy" led to a reform of the German Maternity Protection Act, which came into force on January 1, 2018, and allows female physicians to perform risk-adapted surgery during pregnancy at their own request. However, in Austria, such reform is still pending. The study aimed i) to assess the current situation of how pregnant female surgeons handle their training under the actual restrictive legislature in Austria, especially in context of operative activity, and ii) to identify needs for improvements. Therefore, a nation-wide online survey, initiated by the Austrian Society for Gynecology and Obstetrics and the Young Forum of the Austrian Society of Gynecology and Obstetrics, was performed from June 1 to December 24, 2021, among employed physicians working in surgical specialties. To conduct a general needs assessment, the questionnaire was made available to both female and male physicians in all positions. In total, 503 physicians participated in the survey, of which 70.4% (n = 354) were women and 29.6% (n = 149) were men. The majority of the women (61.3%) were undergoing residency training at the time of their pregnancy. The announcement of the pregnancy to the supervisor(s) occurred on average in the 13th week of gestation (week 2-40). Before that, pregnant female physicians spent an average of 10 h per trimester (first trimester: 0-120 h; second trimester: 0-100 h) in the operating room. The main reason for women to continue surgical activity despite their (yet unreported) pregnancy was "own request". 93% (n = 469) of the participants explicitly wished to be able to perform surgical activities in a safe setting during pregnancy. This response was independent of gender (p = 0.217), age (p = 0.083), specialty (p = 0.351), professional position (p = 0.619), and previous pregnancy (p = 0.142). In conclusion, there is an urgent need to offer female surgeons the possibility of continuing surgical activities during pregnancy. This handling would significantly increase the career opportunities for women who want to build up both a successful career and a family life.

Postgraduate medical education in obstetrics and gynaecology: Where are we now and what do we need for the future? A study on postgraduate training in obstetrics and gynaecology in Germany, Austria and Switzerland.

Objective: In this study, we aim to assess the current situation of postgraduate medical education in obstetrics and gynaecology in Germany, Austria and Switzerland. In addition, we aim to determine transferable advantages amongst the countries. Study design: We performed a survey through a digital questionnaire with a total of 40 questions. The survey was advertised via communication channels of the German, Austrian and Swiss gynaecological societies; the participants were enrolled anonymously. Results: A total of 422 trainees took part in the survey. Differences within the three countries where found regarding the workload and the training of sub-specialties. Generally, the participants described to spend the majority of their daily working hours on documentation. Concerning assessment of current training regulations, more than half of trainees stated that they were actually faced with notable difficulties to fulfil the required obligatory numbers of self-performed interventions being documented. When asked for their intrinsic feeling of safety, around two-third of trainees felt "confident to very confident" during standard interventions. These numbers were up to 12% higher in the group of trainees who experienced simulation training during their education. Conclusion: With the help of this survey, weak points can be identified such as workload and implementation of current training regulations. Projects and ideas as EBCOG PACT, EPAs, the reduction of bureaucracy through digitization and deepening skills through simulation make a valuable contribution to compensate for these deficits and to adapt to future requirements.

Predicting singleton antepartum stillbirth by the demographic Fetal Medicine Foundation Risk Calculator-A retrospective case-control study.

OBJECTIVE: To assess the risk of singleton intrauterine fetal death (IUFD) in women by the demographic setting of the online Fetal Medicine Foundation (FMF) Stillbirth Risk Calculator. METHODS: Retrospective single-centre case-control study involving 144 women having suffered IUFD and 247 women after delivery of a live-born singleton. Nonparametric receiver operating characteristics (ROC) analyses were performed to predict the prognostic power of the FMF Stillbirth risk score and to generate a cut-off value to discriminate best between the event of IUFD versus live birth. RESULTS: Women in the IUFD cohort born a significantly higher overall risk with a median FMF risk score of 0.45% (IQR 0.23-0.99) compared to controls [0.23% (IQR 0.21-0.29); p<0.001]. Demographic factors contributing to an increased risk of IUFD in our cohort were maternal obesity (p = 0.002), smoking (p<0.001), chronic hypertension (p = 0.015), antiphospholipid syndrome (p = 0.017), type 2 diabetes (p<0.001), and insulin requirement (p<0.001). ROC analyses showed an area under the curve (AUC) of 0.72 (95% CI 0.67-0.78; p<0.001) for predicting overall IUFD and an AUC of 0.72 (95% CI 0.64-0.80; p<0.001), respectively, for predicting IUFD excluding congenital malformations. The FMF risk score at a cut-off of 0.34% (OR 6.22; 95% CI 3.91-9.89; p<0.001) yielded an 82% specificity and 58% sensitivity in predicting IUFD with a positive and negative predictive value of 0.94% and 99.84%, respectively. CONCLUSION: The FMF Stillbirth Risk Calculator based upon maternal demographic and obstetric characteristics only may help identify women at low risk of antepartum stillbirth.

Antepartum stillbirth rates during the COVID-19 pandemic in Austria: A population-based study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has had dramatic effects on the pregnant population worldwide, increasing the risk of adverse perinatal outcomes. OBJECTIVE: To assess the incidence of antepartum stillbirth (aSB) during the COVID-19 pandemic in Austria. METHODS: We collected epidemiological data from the Austrian Birth Registry and compared the rate of aSB (i.e., fetal death at or after 24+0 gestational weeks) during the pandemic period (March-December 2020) and in the respective pre-pandemic months (2015-2019). RESULTS: In total, 65 660 pregnancies were included, of which 171 resulted in aSB at 33.7 ± 4.8 gestational weeks. During the pandemic, the aSB rate increased from 2.49‰ to 2.60‰ (P = 0.601), in contrast to the significant decline in preterm deliveries at or before 37 gestational weeks from 0.61‰ to 0.56‰ (relative risk [RR] 0.93; 95% confidence interval [CI] 0.91-0.96; P < 0.001). During the first lockdown, the aSB rate significantly increased from 2.38‰ to 3.52‰ (P = 0.021), yielding an adjusted odds ratio of 1.57 (95% CI 1.08-2.27; P = 0.018). The event of aSB during the COVID-19 pandemic was strongly related with increased fetal weight and maternal obesity. CONCLUSION: In Austria, there has been an overall increase in the incidence of aSB during the pandemic with a significant peak during the first lockdown.

Exposure to night-time light pollution and risk of prolonged duration of labor: A nationwide cohort study.

BACKGROUND: Light pollution (LP) is a ubiquitous environmental agent that affects more than 80% of the world's population. This large nationwide cohort study evaluates whether exposure to LP can influence obstetric outcomes. METHODS: We analyzed Austrian birth registry data on 717 113 cases between 2008 and 2016 and excluded cases involving day-time delivery, <23 + 0 gestational weeks, and/or birthweight <500 g, induction of labor, elective cesarean, or cases with missing data. The independent variable, that is, degree of night-time LP, was categorized as low (0.174 to <0.688 mcd/m2 ), medium (0.688 to <3 mcd/m2 ), or high (3 to <10 mcd/m2 ). Duration of labor and adverse neonatal outcomes served as outcome measures. RESULTS: Cases in regions with high LP (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57) and medium LP (OR, 1.22; 95% CI, 1.14-1.31) showed increased odds of prolonged labor (P < .0001 each). Newborns born in regions with high LP (OR, 1.12; 95% CI, 1.07-1.16) and medium LP (OR, 1.07; 95% CI, 1.04-1.10) showed increased odds of experiencing adverse outcomes (P < .0001 each). Preterm delivery <28 + 0 weeks was also associated with the degree of LP (P = .04). CONCLUSIONS: Night-time LP negatively interferes with obstetric outcomes. The perceived influence of LP as an environmental agent needs to be re-evaluated to minimize associated health risks.

Development of Down Syndrome Research Over the Last Decades-What Healthcare and Education Professionals Need to Know.

Down syndrome (DS) is the most prevalent neurodevelopmental disorder, with a known genetic cause. Besides facial dysmorphologies and congenital and/or acquired medical conditions, the syndrome is characterized by intellectual disability, accelerated aging, and an increased likelihood of an early onset Alzheimer's disease in adulthood. These common patterns of DS are derived from the long-held standard in the field of DS research, that describes individuals with DS as a homogeneous group and compares phenotypic outcomes with either neurotypical controls or other neurodevelopmental disorders. This traditional view has changed, as modern research pinpoints a broad variability in both the occurrence and severity of symptoms across DS, arguing for DS heterogeneity and against a single "DS profile." Nevertheless, prenatal counseling does not often prioritize the awareness of potential within-group variations of DS, portraying only a vague picture of the developmental outcomes of children with DS to expectant parents. This mini-review provides a concise update on existent information about the heterogeneity of DS from a full-spectrum developmental perspective, within an interdisciplinary context. Knowledge on DS heterogeneity will not only enable professionals to enhance the quality of prenatal counseling, but also help parents to set targeted early interventions, to further optimize daily functions and the quality of life of their children.

Densities of decidual high endothelial venules correlate with T-cell influx in healthy pregnancies and idiopathic recurrent pregnancy losses.

STUDY QUESTION: Do high endothelial venules (HEVs) appear in the uterus of healthy and pathological pregnancies? SUMMARY ANSWER: Our study reveals that HEVs are present in the non-pregnant endometrium and decidua parietalis (decP) but decline upon placentation in decidua basalis (decB) and are less abundant in decidual tissues from idiopathic, recurrent pregnancy losses (RPLs). WHAT IS KNOWN ALREADY: RPL is associated with a compromised decidual vascular phenotype. STUDY DESIGN, SIZE, DURATION: Endometrial (n = 29) and first trimester decidual (n = 86, 6-12th week of gestation) tissue samples obtained from endometrial biopsies or elective pregnancy terminations were used to determine the number of HEVs and T cells. In addition, quantification of HEVs and immune cells was performed in a cohort of decidual tissues from RPL (n = 25). PARTICIPANTS/MATERIALS, SETTING, METHODS: Position and frequency of HEVs were determined in non-pregnant endometrial as well as decidual tissue sections using immunofluorescence (IF) staining with antibodies against E-selectin, intercellular adhesion molecule, von Willebrand factor, ephrin receptor B4, CD34 and a carbohydrate epitope specific to HEVs (MECA-79). Immune cell distribution and characterization was determined by antibodies recognizing CD45 and CD3 by IF staining- and flow cytometry-based analyses. Antibodies against c-c motif chemokine ligand 21 (CCL21) and lymphotoxin-beta were used in IF staining and Western blot analyses of decidual tissues. MAIN RESULTS AND THE ROLE OF CHANCE: Functional HEVs are found in high numbers in the secretory endometrium and decP but decline in numbers upon placentation in decB (P ≤ 0.001). Decidua parietalis tissues contain higher levels of the HEV-maintaining factor lymphotoxin beta and decP-associated HEVs also express CCL21 (P ≤ 0.05), a potent T-cell chemoattractant. Moreover, there is a positive correlation between the numbers of decidual HEVs and the abundance of CD3+ cells in decidual tissue sections (P ≤ 0.001). In-depth analysis of a RPL tissue collection revealed a decreased decB (P ≤ 0.01) and decP (P ≤ 0.01) HEV density as well as reduced numbers of T cells in decB (P ≤ 0.05) and decP (P ≤ .001) sections when compared with age-matched healthy control samples. Using receiver-operating characteristics analyses, we found significant predictive values for the ratios of CD3/CD45 (P < 0.001) and HEVs/total vessels (P < 0.001) for the occurrence of RPL. LIMITATIONS, REASONS FOR CAUTION: Analyses were performed in first trimester decidual tissues from elective terminations of pregnancy or non-pregnant endometrium samples from patients diagnosed with non-endometrial pathologies including cervical polyps, ovarian cysts and myomas. First trimester decidual tissues may include pregnancies which potentially would have developed placental disorders later in gestation. In addition, our cohort of non-pregnant endometrium may not reflect the endometrial vascular phenotype of healthy women. Finally, determination of immune cell distributions in the patient cohorts studied may be influenced by the different modes of tissue derivation. Pregnancy terminations were performed by surgical aspiration, endometrial tissues were obtained by biopsies and RPL tissues were collected after spontaneous loss of pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we propose an inherent mechanism by which the endometrium and in particular the decidua control T-cell recruitment. By demonstrating reduced HEV densities and numbers of T cells in decB and decP tissues of RPL samples we further support previous findings reporting an altered vascular phenotype in early pregnancy loss. Altogether, the findings provide important information to further decipher the etiologies of unexplained RPL. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Austrian Science Fund (P31470 B30 to M.K.) and by the Austrian National Bank (17613ONB to J.P.). There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

[Austrian Physical Activity Recommendations for Women during and after Pregnancy, Children of Kindergarten age, Children, and Adolescents]. / Österreichische Bewegungsempfehlungen für Frauen während der Schwangerschaft und danach, für Kinder im Kindergartenalter und für Kinder und Jugendliche.

In this article, based on international recommendations, we present the Austrian physical activity recommendations for women during and after pregnancy, children of kindergarten age, children, and adolescents. For women during pregnancy and in the first months after delivery, the exercise recommendations do not differ from those for adults. Movement restrictions apply only if health problems are present. Children under 6 years of age should engage in a variety of motor tasks for up to 3 hours a day at medium and high intensity levels, so that they can grow up healthy. In the age group of 6 to 18 years of age, daily exercise of at least one-hour duration is recommended. When choosing the type of exercise, the level of development and the activity levels of children and adolescents should be taken into account. The exercise recommendations are intended for dissemination in the field of health promotion and to serve as the basis for the development and evaluation of health-promoting exercise programs in Austria.

The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P<0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83-0.84) and 0.88 (95% CI, 0.83-0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity (P>0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling (P=0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe.

BACKGROUND: Congenital limb malformations are rare, and their perinatal outcomes are not well described. This study analyzed the perinatal outcomes of infants with congenital limb malformations. METHODS: All infants with congenital limb malformations who underwent prenatal assessment and delivery at our tertiary referral center from 2004 through 2017 were retrospectively identified. Neonatal outcome parameters were assessed, and the predictors of worse perinatal outcomes were determined. RESULTS: One hundred twenty-four cases of congenital limb malformations were identified, of which 104 (83.9%) were analyzed. The upper limb was affected in 15 patients (14.4%), the lower limb in 49 (47.1%), and both limbs in 40 (38.5%) patients. A fetal syndrome was identified in 66 patients (63.5%); clubfoot and longitudinal reduction defects were the most frequent malformations. In total, 38 patients (36.5%) underwent termination, seven (6.7%) had stillbirth, and 59 (56.7%) had live-born delivery. Rates of preterm delivery and transfer to the Neonatal Intensive Care Unit were 42.4 and 25.4%, respectively. Localization of the malformation was a determinant of perinatal outcome (P = .006) and preterm delivery (P = .046). CONCLUSIONS: Congenital limb malformations frequently occur bilaterally and are associated with poor perinatal outcomes, including high rates of stillbirth and preterm delivery. Multidisciplinary care and referral to a perinatal center are warranted.

Metabolism of cholesterol and progesterone is differentially regulated in primary trophoblastic subtypes and might be disturbed in recurrent miscarriages.

During pregnancy, extravillous trophoblasts (EVTs) invade the maternal decidua and remodel the local vasculature to establish blood supply for the growing fetus. Compromised EVT function has been linked to aberrant pregnancy associated with maternal and fetal morbidity and mortality. However, metabolic features of this invasive trophoblast subtype are largely unknown. Using primary human trophoblasts isolated from first trimester placental tissues, we show that cellular cholesterol homeostasis is differentially regulated in EVTs compared with villous cytotrophoblasts. Utilizing RNA-sequencing, gene set-enrichment analysis, and functional validation, we provide evidence that EVTs display increased levels of free and esterified cholesterol. Accordingly, EVTs are characterized by increased expression of the HDL-receptor, scavenger receptor class B type I, and reduced expression of the LXR and its target genes. We further reveal that EVTs express elevated levels of hydroxy-delta-5-steroid dehydrogenase 3 beta- and steroid delta-isomerase 1 (HSD3B1) (a rate-limiting enzyme in progesterone synthesis) and are capable of secreting progesterone. Increasing cholesterol export by LXR activation reduced progesterone secretion in an ABCA1-dependent manner. Importantly, HSD3B1 expression was decreased in EVTs of idiopathic recurrent spontaneous abortions, pointing toward compromised progesterone metabolism in EVTs of early miscarriages. Here, we provide insights into the regulation of cholesterol and progesterone metabolism in trophoblastic subtypes and its putative relevance in human miscarriage.

Working-hour phenomenon in obstetrics is an attainable target to improve neonatal outcomes.

BACKGROUND: Giving birth in a health care facility does not guarantee high-quality care or favorable outcomes. The working-hour phenomenon describes adverse outcomes of institutional births outside regular working hours. OBJECTIVES: The objectives of the study were to evaluate whether the time of birth is associated with adverse neonatal outcomes and to identify the riskiest time periods for obstetrical care. STUDY DESIGN: This nationwide retrospective cohort study analyzed data from 2008 to 2016 from all 82 obstetric departments in Austria. Births at ≥ 23+0 gestational weeks with ≥500 g birthweight were included. Independent variables were categorized by the time of day vs night as core time (morning, day) and off hours (evening, nighttime periods 1-4). The composite primary outcome was adverse neonatal outcome, defined as arterial umbilical cord blood pH <7.2, 5 minute Apgar score <7, and/or admission to the neonatal intensive care unit. Multivariate logistic regression was used to develop a model to predict these adverse neonatal outcomes. RESULTS: Of 462,947 births, 227,672 (49.2%) occurred during off hours and had a comparable distribution in all maternity units, regardless of volume (<500 births per year: 50.3% during core time vs 49.7% during off hours; ≥500 births per year: 50.7% core time vs 49.3% off hours; perinatal tertiary center: 51.2% core time vs 48.8% off hours). Furthermore, most women (35.8-35.9%) gave birth between 2:00 and 5:59 am (night periods 3 and 4). After adjustment for covariates, we found that adverse neonatal outcomes also occurred more frequently during these night periods 3 and 4, in addition to the early morning period (night 3: odds ratio, 1.05; 95% confidence interval, 1.03-1.08; P < .001; night 4: odds ratio, 1.08; 95% confidence interval, 1.05-1.10; P < .001; early morning period: odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P < .001). The adjusted odds for adverse outcomes were lowest for births between 6:00 and 7:59 pm (odds ratio, 0.96; 95% confidence interval, 0.93-0.99; P = .006). CONCLUSION: There is an increased risk of adverse neonatal outcomes when giving birth between 2:00 and 7:59 am. The so-called working-hour phenomenon is an attainable target to improve neonatal outcomes. Health care providers should ensure an optimal organizational framework during this time period.

Human trophoblast invasion: new and unexpected routes and functions.

Until recently, trophoblast invasion during human placentation was characterized by and restricted to invasion into uterine connective tissues and the uterine spiral arteries. The latter was explained to connect the arteries to the intervillous space of the placenta and to guarantee the blood supply of the mother to the placenta. Today, this picture has dramatically changed. Invasion of endoglandular trophoblast into uterine glands, already starting at the time of implantation, enables histiotrophic nutrition of the embryo prior to perfusion of the placenta with maternal blood. This is followed by invasion of endovenous trophoblasts into uterine veins to guarantee the drainage of fluids from the placenta back into the maternal circulation throughout pregnancy. In addition, invasion of endolymphatic trophoblasts into the lymph vessels of the uterus has been described. Only then, invasion of endoarterial trophoblasts into spiral arteries takes place, enabling hemotrophic nutrition of the fetus starting with the second trimester of pregnancy. This new knowledge paves the way to identify changes that may occur in pathological pregnancies, from tubal pregnancies to recurrent spontaneous abortions.

Pregnancy-associated diamine oxidase originates from extravillous trophoblasts and is decreased in early-onset preeclampsia.

Human extravillous trophoblast (EVT) invasion of the pregnant uterus constitutes a pivotal event for the establishment of the maternal-fetal interface. Compromised EVT function manifesting in inadequate arterial remodeling is associated with the severe pregnancy disorder early-onset preeclampsia (eoPE). Recent studies suggest that EVTs invade the entire uterine vasculature including arteries, veins and lymphatics in the first trimester of pregnancy. We therefore hypothesized that EVT-derived factors accumulate in the circulation of pregnant women early in gestation and may serve to predict eoPE. In contrast to published literature, we demonstrate that placenta-associated diamine oxidase (DAO) is not expressed by maternal decidual cells but solely by EVTs, especially when in close proximity to decidual vessels. Cultures of primary EVTs express and secret large amounts of bioactive DAO. ELISA measurements indicate a pregnancy-specific rise in maternal DAO plasma levels around gestational week (GW) 7 coinciding with vascular invasion of EVTs. Strikingly, DAO levels from eoPE cases were significantly lower (40%) compared to controls in the first trimester of pregnancy but revealed no difference at mid gestation. Furthermore, DAO-containing pregnancy plasma rapidly inactivates pathophysiologically relevant histamine levels. This study represents the first proof of concept suggesting EVT-specific signatures as diagnostic targets for the prediction of eoPE.

Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions.

STUDY QUESTION: Do extravillous trophoblasts (EVTs) invade non-arterial decidual vessels in healthy and pathological pregnancies? SUMMARY ANSWER: Our results reveal that trophoblast invasion of venous and lymphatic vessels is a frequent event during the first trimester of pregnancy and is compromised in  recurrent spontaneous abortion (RSA). In addition, the present data suggest that EVTs populate regional lymph nodes during pregnancy. WHAT IS ALREADY KNOWN: Human trophoblasts remodel and invade decidual spiral arteries. In addition, a recent report demonstrates that trophoblasts contact and invade decidual veins. STUDY DESIGN, SIZE, DURATION: Tissue samples of human first trimester deciduae basalis (n = 54, 6th-13th weeks of gestation) obtained from elective pregnancy terminations were used to study trophoblast invasion into veins and lymphatics, in comparison to arteries. Age-matched cases of idiopathic, recurrent spontaneous abortions tissue samples (n = 23) were assessed for cell numbers of EVTs in these decidual vessels. In addition, lymph nodes of four pregnant women were analysed for the presence of EVTs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Localization, frequency and EVT-mediated targeting and invasion of arterial, venous as well as lymphatic vessels were determined in first trimester decidua basalis tissue sections using immunofluorescence staining with antibodies against CD31, CD34, ephrin B2 (EFNB2), ephrin receptor B4 (EPHB4), HLA-G, podoplanin, prospero-related homeobox 1 (Prox-1), alpha-smooth muscle actin 2 (ATCTA2), von willebrand factor (vWF) and proteoglycan 2 (PRG2). Arterial, venous and lymphatic-associated EVTs were further characterized according to their position in the vascular structure and classified as intramural (im) or intraluminal (il). MAIN RESULTS AND THE ROLE OF CHANCE: EVTs, specifically expressing PRG2, target and invade veins and lymphatics in first trimester decidua basalis since HLA-G+ trophoblast were detected in the vascular wall (intramural EVT, imEVTs) and in the lumen of these vessels (intraluminal EVT, ilEVTs). In total, 276 arteries, 793 veins and 113 lymphatics were analysed. While EVTs contact and invade arteries and veins to a similar extent we found that lymphatics are significantly less affected by EVTs (P = 0.001). Moreover, ilEVTs were detected in the lumen of venous and lymphatic vessels, whereas ilEVTs were only found occasionally in the lumen of arteries. Interestingly, RSA tissue sections contained significantly more arterial (P = 0.037), venous (P = 0.002) and lymphatic vessels (P < 0.001), compared to healthy controls. However, while RSA-associated arterial remodeling was unchanged (P = 0.39) the ratios of EVT-affected versus total number of veins (P = 0.039) and lymphatics (P < 0.001) were significantly lower in RSA compared to age-matched healthy decidual sections. Finally, HLA-G+/PRG2+/CD45-EVTs can be detected in regional lymph nodes of pregnant women diagnosed with cervical cancer. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, first trimester decidual tissues from elective terminations of pregnancies have been examined and used as a reference for healthy pregnancy. However, this collective may also include pregnancies which would have developed placental disorders later in gestation. Due to limitations in tissue availability our staining results for EVT-specific marker expression in regional lymph nodes of pregnant women are based on four cases only. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we propose migration of HLA-G+ cells into regional lymph nodes during pregnancy suggesting that the human EVT is capable of infiltrating maternal tissues via the blood stream. Moreover, the description of compromised EVT invasion into the venous and lymphatic vasculature in RSA may help to better understand the pathological characteristics of idiopathic recurrent pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Austrian Science Fund (grant P-25187-B13 to J.P. and grant P-28417-B30 to M.K.). There are no competing interests to declare.

The fibrinogen/CRP ratio as a new parameter for the diagnosis of disseminated intravascular coagulation in patients with HELLP syndrome and as a predictive factor for neonatal outcome.

OBJECTIVE: The aim of this study was to determine if the fibrinogen/C-reactive protein (CRP) ratio could be used in obstetrics as a predictor for a disseminated intravascular coagulation. STUDY DESIGN: One hundred eleven patients with hemolysis, elevated liver enzymes, and low platelet count syndrome at the Department of Obstetrics and Fetomaternal Medicine (General Hospital, Vienna, Austria) were selected and divided into 2 groups (overt disseminated intravascular coagulation, no overt disseminated intravascular coagulation). The classical parameters and the fibrinogen/CRP ratio were compared. The analysis was carried out using IBM SPSS statistical package (SPSS, Inc, Cary, NC). RESULTS: The fibrinogen/CRP ratio showed significant differences. The receiver-operating characteristic analysis showed for the ratio (area under the curve, 0.74) significantly better discriminative power than for fibrinogen (area under curve, 0.59). The odds ratio for the fibrinogen/CRP ratio was 7.04. Finally, significant correlations between the ratio and the neonatal outcome were found. CONCLUSION: We suggest the implementation of the fibrinogen/CRP ratio within patients with hemolysis, elevated liver enzymes, and low platelet count syndrome as a diagnostic and prognostic factor for the occurrence of disseminated intravascular coagulation.