Quality of analgesic care in labor: A cross-sectional study of the first national register-based benchmarking system.

OBJECTIVE: Unlike other types of acute pain, labor pain is considered physiological. Due to the heterogeneous management during labor, there is a lack of intention to define quality of care of peripartal analgesia. This study presents the first results of the national register for this evaluation. METHODS: This prospective cross-sectional study, conducted in five different German level-three hospitals, included women after vaginal childbirth between January 2020 and January 2022. A validated questionnaire was completed 24 h postpartum, including information about labor pain, satisfaction, and expectations regarding analgesia. Data were centrally recorded with obstetric records using the database of the QUIPS (Quality Improvement in Postoperative Pain Management) Project. RESULTS: A total of 514 women were included. On an 11-point Numerical Rating Scale, pain intensity during labor was severe (8.68 ± 1.8) while postpartal pain was 3.9 (±2.1). The second stage of labor was considered the most painful period. Only 62.6% of the parturients obtained pharmacological support, with epidural being the most effective (reduction of 3.8 ± 2.8 points). Only epidural (odds ratio [OR] 0.22) and inhalation of nitrous oxide (OR 0.33) were protective for severe pain. In benchmarking, a relation between satisfaction, pain intensity, and the use of epidural was found; 40.7% of the women wished they had received more analgesic support during labor. CONCLUSION: This study highlights deficiencies in analgesic management in high-level perinatal centers, with more than 40% of parturients considering actual practices as insufficient and wishing they had received more analgesic support, despite the availability of analgesic options. Using patient-reported outcomes can guarantee qualitative tailored analgesic care in women.

Peripartal pain perception and pain therapy: introduction and validation of a questionnaire as a quality instrument.

BACKGROUND: Labor pain is difficult to measure. The aim of this proof-of-concept study is to implement and test a questionnaire assessing pain sensation during and after vaginal deliveries. Its key aspect is a highly standardized survey of patient-reported outcome (PRO) by staff not involved in routine care. METHODS: Between January and November 2015 339 women were assessed 24-48 h after spontaneous or operative-vaginal delivery of a singleton. German language skills were a prerequisite to participate. The test-retest reliability was calculated in 38 women 24-36 and 48-72 h postpartum between July and October 2017. Primiparae after spontaneous delivery and multiparae with no history of operative deliveries were compared in a subgroup analysis. RESULTS: Maximum labor pain and post-partum pain were reported a median of 9 [8-10] and 4 [3-6]. Higher ratings were associated with younger age, higher gestational ages, infant's biometrics, and the duration of laboring. Only regional analgesia tended to reduce pain perception (NRS 8 vs. 9). Higher-degree injuries were associated with less pain postpartum. The questionnaire proved to be reliable in most aspects (Cronbach's α > 0.6 for 19/21 questions) and showed an acceptable content and criterion validity (Cohen correlation > ± 0.3, interrelation between items). CONCLUSION: Labor is a very painful experience, irrespective of previous obstetric history. Ratings indicate inadequateness of treatment except for patients receiving preventive postoperative pain management. Systematic postpartum pain assessment, hence, is still a pending issue. Adjustments will be made concerning language skills and specific questions on effectiveness of analgesia otherwise good reliability and validity of the questionnaire were proven.

Ex vivo human placental transfer study on recombinant Von Willebrand factor (rVWF).

Deficiency or mutation of von Willebrand factor (VWF) leads to a coagulation disorder (von Willebrand disease; VWD) which requires a lifelong therapy. For avoiding maternal complications treatment may be necessary also in pregnancy, but placental transfer to the fetus might impact its coagulation system and evoke undesired side effects. As VWF is a very large molecule it may be assumed that it does not pass the placental barrier. To prove this hypothesis the materno-fetal transfer of recombinant VWF (rVWF) has been analyzed ex vivo in a total of 21 valid dual side placenta perfusions. Three groups of five placentas each have been perfused with physiological and up to ten-fold increased concentrations of rVWF for 2 h. Six placentas have been used for control perfusions. A series of different control parameters has been assessed for documentation of intactness and functionality of the placenta and the perfusion system. In not a single analysis, independent of time and concentration, rVWF was detected in the fetal circuit. In the maternal circuit VWF concentration decreased slightly during perfusion. These results demonstrate that recombinant VWF does not pass the human placenta.

Does Pentaerytrithyltetranitrate reduce fetal growth restriction in pregnancies complicated by uterine mal-perfusion? Study protocol of the PETN-study: a randomized controlled multicenter-trial.

BACKGROUND: Affecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function and consequent mal-perfusion of the placenta is the leading cause of FGR. Although, screening for placental insufficiency based on uterine artery Doppler measurement is well established, there is no treatment option for pregnancies threatened by FGR. The organic nitrate pentaerithrityl tetranitrate (PETN) is widely used for the treatment of cardiovascular disease and has been shown to have protective effects on human endothelial cells. In a randomized placebo controlled pilot-study our group could demonstrate a risk reduction of 39% for the development of FGR, and FGR or death, by administering PETN to patients with impaired uterine artery Doppler at mid gestation. To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated. METHOD: The trial has been initiated in 14 centres in Germany. Inclusion criteria are abnormal uterine artery Doppler, defined by mean PI > 1.6, at 190 to 226 weeks of gestation in singleton pregnancies. Included patients will be monitored in 4-week intervals. Primary outcome measures are development of FGR (birth weight < 10th percentile), severe FGR (birth weight < 3rd centile) and perinatal death. Placental abruption, birth weight below the 3rd, 5th and 10th centile, development of FGR requiring delivery before 34 weeks` gestation, neonatal intensive care unit admission, and spontaneous preterm delivery < 34 weeks` and 37 weeks` gestation will be assessed as secondary endpoints. Patient enrolment was started in August 2017. Results are expected in 2020. DISCUSSION: During the past decade therapeutic agents with possible perfusion optimizing potential have been evaluated in clinical trials to treat FGR. Meta-analysis and sub-analysis of trials targeting preeclampsia revealed ASS to have a potential in reducing FGR. Phosphodiesterase-type-5 inhibitors have recently been tested in a worldwide RCT for therapy of established FGR, failing to show an effect on neonatal outcome. The ongoing multicenter trial will, by confirming our previous results, finally provide a therapeutic option in cases at risk for FGR. TRIAL REGISTRATION: DRKS00011374 registered at September 29th, 2017 and NCT03669185 , registered September 13th, 2018.

Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of placental alpha microglobulin-1 (PAMG-1), fetal fibronectin (fFN) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) tests in predicting spontaneous preterm birth (sPTB) within 7 days of testing in women with symptoms of preterm labor, through a systematic review and meta-analysis of the literature. The test performance of each biomarker was also assessed according to pretest probability of sPTB ≤ 7 days. METHODS: The Cochrane, MEDLINE, PubMed and ResearchGate bibliographic databases were searched from inception until October 2017. Cohort studies that reported on the predictive accuracy of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB within 7 days of testing in women with symptoms of preterm labor were included. Summary receiver-operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive (LR+) and negative (LR-) likelihood ratios were generated using indirect methods for the calculation of pooled effect sizes with a bivariate linear mixed model for the logit of sensitivity and specificity, with each diagnostic test as a covariate, as described by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. RESULTS: Bivariate mixed model pooled sensitivity of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB ≤ 7 days was 76% (95% CI, 57-89%), 58% (95% CI, 47-68%) and 93% (95% CI, 88-96%), respectively; pooled specificity was 97% (95% CI, 95-98%), 84% (95% CI, 81-87%) and 76% (95% CI, 70-80%) respectively; pooled PPV was 76.3% (95% CI, 69-84%) (P < 0.05), 34.1% (95% CI, 29-39%) and 35.2% (95% CI, 31-40%), respectively; pooled NPV was 96.6% (95% CI, 94-99%), 93.3% (95% CI, 92-95%) and 98.7% (95% CI, 98-99%), respectively; pooled LR+ was 22.51 (95% CI, 15.09-33.60) (P < 0.05), 3.63 (95% CI, 2.93-4.50) and 3.80 (95% CI, 3.11-4.66), respectively; and pooled LR- was 0.24 (95% CI, 0.12-0.48) (P < 0.05), 0.50 (95% CI, 0.39-0.64) and 0.09 (95% CI, 0.05-0.16), respectively. The areas under the ROC curves for PAMG-1, fFN and phIGFBP-1 for sPTB ≤ 7 days were 0.961, 0.874 and 0.801, respectively. CONCLUSIONS: In the prediction of sPTB within 7 days of testing in women with signs and symptoms of preterm labor, the PPV of PAMG-1 was significantly higher than that of phIGFBP-1 or fFN. Other diagnostic accuracy measures did not differ between the three biomarker tests. As prevalence affects the predictive performance of a diagnostic test, use of a highly specific assay for a lower-prevalence syndrome such as sPTB may optimize management. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

N-cadherin knockdown leads to disruption of trophoblastic and endothelial cell interaction in a 3D cell culture model - New insights in trophoblast invasion failure.

INTRODUCTION: Trophoblast homing to maternal spiral arteries is mandatory for successful placentation. Cell-cell adhesion molecules regulate this process and adhesion molecule expression is altered in impaired placentation. We hypothesize that, similar to immune cell recruitment, trophoblast cell adherence and rolling are primarily mediated by adhesion molecules like, cadherins, immunoglobulins, selectins and their partnering ligands. Here, the interdependence of adhesion molecule expression in trophoblastic cell lines of diverse origin was investigated in relation to their interaction with endothelial cell networks on Matrigel® co-cultures and the effect of specific adhesion molecule knockdown analyzed. METHODS: Trophoblastic cells were labeled in red and co-cultured with green HUVEC networks on Matrigel®. Association was quantified after collection of fluorescence microscopy pictures using Wimasis® internet platform and software. Expression of adhesion molecules was analyzed by PCR and Western blot, immuno-fluorescence and flow cytometry. The impact of adhesion molecules on trophoblast-endothelial-cell interaction was investigated using siRNA technique. RESULTS: N-cadherin and CD162 were specifically expressed in the trophoblast cell line HTR-8/SVneo, which closely adhere to and actively migrate toward HUVEC networks on Matrigel®. Suppression of N-cadherin led to a significant alteration in trophoblast-endothelial cell interaction. Expression of VE-cadherin in closely interacting trophoblast cells was not confirmed in vitro. DISCUSSION: We identified N-cadherin to mediate specific interaction between HUVEC and the migrating trophoblast cells HTR-8/SVneo in a Matrigel® co-culture model. VE-cadherin contribution could not be confirmed in vitro. Our results support the hypothesis that impaired N-cadherin but not VE-cadherin expression is involved in trophoblast recruitment to the maternal endothelium.

The "killer cell story" in recurrent miscarriage: Association between activated peripheral lymphocytes and uterine natural killer cells.

Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls. Finally, n=147 idiopathic RM (iRM) and n=121 non-iRM patients were identified. Peripheral blood levels of CD45+CD3-CD56+CD16+ NK cells were determined in non-pregnant patients and controls in the mid-luteal phase by FACS. In n=129 RM patients a uterine biopsy was taken to evaluate CD56+ NK cells by immunohistochemistry. PRM showed higher absolute pNK than sRM (median/µl (Q1;Q3): 234 (147;306) vs 176 (128;245), p=0.02). Further a trend towards higher pNK percentages in pRM was detected. UNK numbers did not differ between RM subgroups and did not correlate with pNK. However, the rate of highly elevated uNK was increased in iRM compared to non-iRM patients (p=0.04). Further, higher numbers of CD45+CD3-DR+ (p<0.01) and CD45+CD3+CD8+DR+ (p=0.04) peripheral lymphocytes were associated with higher uNK numbers. In conclusion, elevated pNK were present in pRM patients. Although pNK and uNK numbers did not correlate, the association between high CD45+CD3-DR+ and CD45+CD3+CD8+DR+ peripheral lymphocytes and uNK might indicate that activated NK, B and T cells provide cytokines for the differentiation of uNK.

Knowledge and Implementation of the S3 Guideline on Gestational Diabetes among Gynecologists and Diabetologists Four Years after Publication: Results of a Survey of 773 Gynecologists and 76 Diabetologists on their Knowledge of the Guideline on Gestational Diabetes (AWMF 057-008, 2011).

BACKGROUND: An S3 guideline on the diagnosis and differentiated management of gestational diabetes (GDM) was published in Germany in 2011. This guideline replaced the previously applicable recommendations for the diagnosis and treatment of GDM and, for the first time, compiled evidence-based recommendations for the care of patients with GDM. The new guideline has focused particularly on the counselling offered to all patients with GDM about the associated long-term health risks. In this study we investigated the state of knowledge about the guideline among gynecologists and diabetologists in Thuringia and Lower Saxony. METHOD: A questionnaire with 23 questions was sent out to 773 gynecologists and 76 diabetologists providing outpatient care in Lower Saxony and Thuringia. The statistical analysis was descriptive and inferential for comparisons between groups. RESULTS: The response rate was 54 %; an average of 47.6 % of the individual questions were answered correctly in the completed questionnaires. The questions were answered correctly significantly more frequently by persons in the group with a good knowledge of the guidelines (75 vs. 61 %, p < 0.001). There were no significant differences between groups when differences between federal states or medical specialties were compared. CONCLUSIONS: The results of our study show a good general state of knowledge of the guideline and point to a high level of willingness to implement the recommendations of the S3 guideline on GDM. With regard to the follow-up care provided to patients with GDM and depression, this study found a significant need for further training.

Assessment of fetal maturation age by heart rate variability measures using random forest methodology.

Fetal maturation age assessment based on heart rate variability (HRV) is a predestinated tool in prenatal diagnosis. To date, almost linear maturation characteristic curves are used in univariate and multivariate models. Models using complex multivariate maturation characteristic curves are pending. To address this problem, we use Random Forest (RF) to assess fetal maturation age and compare RF with linear, multivariate age regression. We include previously developed HRV indices such as traditional time and frequency domain indices and complexity indices of multiple scales. We found that fetal maturation was best assessed by complexity indices of short scales and skewness in state-dependent datasets (quiet sleep, active sleep) as well as in state-independent recordings. Additionally, increasing fluctuation amplitude contributed to the model in the active sleep state. None of the traditional linear HRV parameters contributed to the RF models. Compared to linear, multivariate regression, the mean prediction of gestational age (GA) is more accurate with RF than in linear, multivariate regression (quiet state: R(2)=0,617 vs. R(2)=0,461, active state: R(2)=0,521 vs. R(2)=0,436, state independent: R(2)=0,583 vs. R(2)=0,548). We conclude that classification and regression tree models such as RF methodology are appropriate for the evaluation of fetal maturation age. The decisive role of adjustments between different time scales of complexity may essentially extend previous analysis concepts mainly based on rhythms and univariate complexity indices. Those system characteristics may have implication for better understanding and accessibility of the maturating complex autonomic control and its disturbance.

[Progesterone for Prevention of Preterm Birth--Evidence-based Indications]. / Progesteron zur Prävention der Frühgeburt--Evidenz-basierte Indikationen.

BACKGROUND: The prevention and treatment of preterm birth remains an unsolved problem in modern obstetrics. Progesterone has a variety of actions on the myometrium and the cervix, among others inhibition of myometrial contractility and a cervix strengthening effect by inhibiting the production of proinflammatory cytokines and prostaglandins as well as by reducing the synthesis of proteins, which play a crucial role in initiating labour. Consequently, progesterone may be a promising candidate for the prevention of preterm birth. MATERIAL AND METHODS: We searched PubMed from 1956 to August 2014 using a combination of key words and text words related to preterm birth and progesterone. ('progesterone', progestins, 17-OHPC). The aim of the literature search was to determine evidence-based indications for the use of progesterone in the prevention of preterm birth. RESULTS: (i) Patients with a singleton pregnancy and history of preterm birth should receive vaginal progesterone daily (200 mg capsule or 90 mg containing gel) from 16+0 to 36+0 weeks of gestation (alternatively 250 mg intramuscular 17-OHPC weekly): level of evidence 1a, grade of recommendation ++ . Prophylactic progesterone reduces the incidence of preterm birth <34 and <37 weeks of gestation and perinatal mortality significantly. (ii) Patients with singleton pregnancies and a sonographically short cervix (≤25 mm) before 24 weeks of gestation should receive vaginal progesterone daily (200 mg capsule or 90 mg containing gel) until 36+6 weeks of gestation: level of evidence 1a, grade of recommendation ++ . Prophylactic progesterone leads to a significant reduction in the incidence of preterm birth <28, <33, and <35 weeks of gestation and is associated with a significant reduction of neonatal morbidity. (III) There is a lack of evidence to recommend vaginal progesterone or intramuscular 17-OHPC for primary tocolysis or for "adjunctive" tocolysis (in combination with conventional tocolytic agents). (IV) There is a growing body of evidence that vaginal progesterone (400 mg/day) after successful tocolysis ("maintenance therapy") is a promising option for prolongation of pregnancy: level of evidence 1b, grade of recommendation +. (V) Data from the literature are insufficient to recommend progesterone in patients with preterm rupture of membranes or in the perioperative management of patients requiring transvaginal cervical cerclage. (VI) The vaginal administration of progesterone is well-tolerated by the patients and has only minor maternal side effects, whereas intramuscular injections of 17-OHPC are associated with a significant higher rate of side effects (e. g. local pain, nausea, diarrhoea). It is mandatory to inform patients on the off-label use of progesterone in pregnancy. DISCUSSION: Prophylactic progesterone administration is an evidence-based method for the prevention of preterm birth in women with a previous preterm birth and in pregnant women with a sonographically short cervix (≤25 mm) before 24 weeks of gestation. Vaginal progesterone is favoured over intramuscularly applied 17-OHPC, especially because of the lower rate of maternal side effects. Whether progesterone is an effective approach for the treatment of preterm birth as a tocolytic agent (primary, adjunctive) or for maintenance therapy after arrest of preterm labour has to be shown in further well-designed randomised and controlled trials with adequate statistical power.

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?

Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.

Sequential use of double-balloon catheter and oral misoprostol versus oral misoprostol alone for induction of labour at term (CRBplus trial): a multicentre, open-label randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of inducing labour using a double-balloon catheter and oral misoprostol sequentially, in comparison with oral misoprostol alone. DESIGN: A multicentre randomised controlled trial. SETTING: Five hospitals in Germany. POPULATION: A total of 326 pregnant women with an unfavourable cervix undergoing labour induction at term. METHODS: Women were randomly assigned according to a computer-generated allocation sequence to sequential use of double-balloon catheter and oral misoprostol (study group) or oral misoprostol alone (control group). In the study group, the double-balloon catheter was used the first day before starting oral misoprostol the second day. MAIN OUTCOME MEASURES: The primary outcome measure was the induction-to-delivery interval, and a further outcome parameter was delivery within 48 hours. RESULTS: The median times for induction of labour until delivery were 32.4 hours in the study group and 22.5 hours in the control group (P = 0.004). This difference was not seen when evaluating according to parity (nulliparous, P = 0.19; parous, P = 0.06). The rate of vaginal delivery within 48 hours did not differ between both groups. The number of applications of misoprostol (two versus three, P < 0.001) and the dose of misoprostol used was lower in the study group (100 versus 200 µg, P < 0.001). In the study group, there were more Apgar scores of <7 at 5 minutes (8 versus 1, P = 0.04). CONCLUSIONS: The use of a double-balloon catheter on the first day, before starting oral misoprostol on the second day, did not improve the induction to delivery interval and the rate of delivery within 48 hours, in comparison with oral misoprostol alone.

Developing fetal motor-cardiovascular coordination analyzed from multi-channel magnetocardiography.

Fetal movements (FM) related heart rate accelerations (AC) are an important maturation criterion. Since Doppler-based time resolution is not sufficient for accompanying heart rate variability analysis, the work is aimed at a comprehensive FM-AC analysis using magnetocardiographic recordings from fetuses during sleep.We identify FM and AC by independent component analysis and automatic recognition algorithms. We investigate associations between FM and AC of different magnitude by means of event coincidence and time series cross-correlation over the maturation period of 21-40 weeks of gestation (WGA).FM related AC appear with increasing AC magnitude and WGA. Vice versa, AC related FM appear independent of WGA, but more frequently with increasing AC amplitude. The FM-AC correlation exists already at 21 WGA and further increases with WGA while the variability of its time delay decreases. Hence, FM and AC are clearly associated over the whole investigated maturation period. The increase of FM related AC runs parallel to the increasing AC magnitude.The MCG methodology was confirmed and results from previous Doppler-based analyses reproduced. Hence, MCG recordings allow the collective analysis of heart rate variability based maturation indices and FM related AC. This synergism may improve the diagnosis of fetal developmental disorders.

[Prevention of preterm birth by Shirodkar cerclage--clinical results of a retrospective analysis]. / Klinische Ergebnisse der Cerclage nach Shirodkar bezüglich der Prävention der Frühgeburtlichkeit--eine retrospektive Analyse.

In spite of the continuous progress in prenatal care, 1 out of 10 babies is born too early--tendency rising worldwide. As a consequence of the heterogeneous aetiology of preterm birth, there is still no single and efficient interventional therapy. Cerclage is one option for pregnancies with cervical insufficiency, whereas the clinical benefit is discussed controversially. We analyzed in a retrospective study with 120 patients the effect of a cerclage intervention regarding pregnancy prolongation. Patients with cervical incompetence and Shirodkar cerclage were compared to those undergoing conservative treatment. As expected, gestational age at delivery was significantly lower after emergency cerclage (31 weeks) compared to prophylactic (36 weeks) and therapeutic cerclage (35 weeks). Prolongation differs significantly between the prophylactic (18 weeks), therapeutic (14 weeks) and emergency cerclage (10 weeks) groups. Conservative management achieved 8 weeks prolongation. Of note, particularly emergency cerclage in cases with advanced cervical incompetence resulted in a substantially higher pregnancy prolongation (10 weeks) compared to no intervention (one week). The efficiency of cerclage operations has to be assessed in a differentiated manner based on the clinical situation and indication. The clinical benefit depends strongly on proper patient selection.

[Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland)]. / Management der postpartalen Blutung (PPH): Algorithmus der Interdisziplinären D-A-CH-Konsensusgruppe PPH (Deutschland - Österreich - Schweiz).

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.

Sonographic discrimination between benign and malignant adnexal masses in premenopause.

PURPOSE: The aim of this study was to assess the diagnostic value of sonographic pattern recognition by experts, a standardized morphological scoring system, the risk malignancy index (RMI) and CA 125 assay for the preoperative assessment of ovarian lesions in premenopausal patients. MATERIAL AND METHODS: Diagnostic work-up of 1320 patients who underwent surgical exploration due to an adnexal mass at a tertiary referral center were included. We assessed the discriminative value of pattern recognition, a sonographic morphological scoring system, RMI and CA 125 by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa for each diagnostic approach while using histopathology as the reference standard. RESULTS: Pattern recognition showed the highest discriminative power with an observed kappa of 0.53. Sensitivity and specificity yielded 0.76 and 0.97 respectively. Combining pattern recognition with CA 125 serum measurement in the context of a triage system diminished the diagnostic value (kappa: 0.24; sensitivity: 0.29 specificity: 0.97). For the RMI we observed a sensitivity of 0.54 and a specificity of 0.96 and estimated kappa value yielded 0.37. Omitting the CA 125 assay and using a morphological sonographic assessment system increased the kappa value to 0.45 with sensitivity and specificity observed at 0.61 and 0.97 respectively. CONCLUSION: Expert pattern recognition was found to be the method with the highest discriminative power in assessing an adnexal mass during premenopause. Additional assessment of serum CA 125 diminished the diagnostic accuracy. Standardized morphological sonographic assessment resulted in a moderate diagnostic accuracy. Supplementing the morphological sonographic assessment with CA 125 by using the RMI algorithm did not improve the diagnostic value.

eNOSI4 and EPHX1 polymorphisms affect maternal susceptibility to preeclampsia: analysis of five polymorphisms predisposing to cardiovascular disease in 279 Caucasian and 241 African women.

PURPOSE: The aim of this study was to evaluate possible associations of genetic polymorphisms predisposing to cardiovascular disease with the development and/or the severity of preeclampsia. METHODS: A two hospital-based prospective case-control study was performed in Germany and Ghana. 470 blood samples of 250 Caucasian and 220 black African have been genotyped by pyrosequencing and fragment length analysis. We evaluated the distribution of the epoxide hydrolase 1 (EPHX1) polymorphism on exon 3, the endothelial nitric oxide synthase (eNOS) polymorphisms on exon 7 and on intron 4, the angiotensinogen polymorphism on exon 2 and the estrogen receptor 1 polymorphism in intron 1. RESULTS: 74 Caucasian and 84 African were classified as preeclampsia with 27 Caucasian developing a hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and 17 African women experiencing eclampsia. Multivariate logistic regression analysis adjusting for ethnicity, age and parity revealed for carriers of eNOSI4 VNTR4a a 1.7-fold increased (95% CI 1.10-2.711, p = 0.016) risk to develop preeclampsia and a 3.6-fold increase for carriers of the EPHX1 113Tyr (95% CI 1.366-8.750, p = 0.009) to develop severest preeclampsia. CONCLUSION: Our finding of eNOSI4 polymorphism predisposing to preeclampsia independently of ethnicity, age and parity supports the concept of NO being involved in the endothelial disorder preeclampsia. Since EPHX1 is highly expressed in the liver, can interact with various signaling pathways and is involved in central nervous system disorders, the association of EPHX1 polymorphism with the HELLP syndrome and eclampsia may hint to EPHX being a further key player in the pathogenesis of preeclampsia.