[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.

Comparison of three first trimester screening algorithms for trisomy 21 with and without adjustment for maternal characteristics.

PURPOSE: Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics. MATERIALS AND METHODS: Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free ß-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status. RESULTS: Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 - 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg. CONCLUSION: Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.

[Megacystis-microcolon intestinal hypoperistalsis syndrome (MMIHS) as a rare differential diagnosis of foetal megacystis on ultrasonography]. / Megacystis-Microcolon intestinales Hypoperistaltik-Syndrom (MMIHS) als seltene Differenzialdiagnose bei fetaler Megacystis im Ultraschall.

INTRODUCTION: Foetal megacystis (incidence 1:1 500) occurring in the first trimester may already be a sign of congenital malformation. Often, urethral valves are causally responsible in male foetuses far more frequently than urethral atresia. As a further differential diagnosis, the "prune-belly syndrome" needs to be distinguished. Far more difficult to classify prenatally is the rare MMIHS which, in contrast to the diagnosis of urethral valves, is associated with an unfavourable prognosis. CASE REPORT: This is a report on a 28-year-old IG/0P, whose foetus of 26+4 gestational weeks was found on ultrasonography for the first time to have a megacystis of 48 mm diameter and bilateral hydronephrosis. The female foetus was surrounded by a normal amount of amniotic fluid which, during the further course of the pregnancy, developed into polyhydramnios. The serial puncture of the urinary bladder showed a normal karyotype and no impairment of the renal concentrating capacity or of protein loss. By reason of an immense enlargement of the abdomen due to the 100 mm large urinary bladder, a Caesarean section was conducted at 36+0 gestational weeks. A catheter could be inserted into the urinary bladder postpartum easily. However, nourishment was not possible and after radiological examination, MMIHS was diagnosed. CONCLUSION: In the case of a foetal megacystis detected by ultrasonography, especially associated with polyhydramnios and female gender, the rare MMIHS, which is infaust, should be taken into consideration.

The accuracy of BI-RADS classification of breast ultrasound as a first-line imaging method.

PURPOSE: The aim was to evaluate the accuracy of BI-RADS categories 3 - 5 in breast ultrasound (US) as the first-line imaging method. MATERIALS AND METHODS: 5077 examinations of a consecutive, unselected and mixed collective of symptomatic and asymptomatic patients were performed. Of these examinations, 835 cases of BIRADS 3 - 5 could be analyzed. RESULTS: The PPV with respect to a malignant lesion for BI-RADS 3, 4, 5 was 0.03, 0.48, and 0.97, respectively. When BI-RADS 4 and 5 cases are considered to be suspicious, the ratio of benign to malignant findings corresponds to 1:1.8. Analyzing BIRADS 3 - 5 lesions, the sensitivity, specificity and accuracy are 0.92, 0.85, and 0.87, respectively. CONCLUSION: The data support the feasibility of US for discriminating malignant from benign findings corresponding to the ACR BI-RADS classification without excessively increasing the number of unnecessary biopsies.

[Late preterms: the influence of foetal gender on neonatal outcome]. / Late preterms: Auswirkungen des fetalen Geschlechts auf das neonatologische Outcome.

BACKGROUND: The group of the so-called late preterms (infants born at 34 0/7-36 6/7 weeks gestational age) has been underestimated with respect to their neonatal outcome. Among infants born before the 29th week of pregnancy, a gender-specific difference in favour of females regarding morbidity became evident. The aim of this study is to investigate whether these findings are transferable to the group of late preterms. METHODS: The neonatal outcome of 528 consecutive singletons, born at 34 0/7-36 6/7 weeks gestational age and requiring intensive care, was examined. RESULTS: Neonatal complications have been particularly analysed with regard to gender-specific differences. Boys (n=292) were significantly more frequently affected by sepsis (3.8 vs. 0.9%; p=0,0314, x²-test). Girls had significantly longer stays in the neonatal intensive care unit (median 12 (Q1:8; Q3:17) vs. 11 (6;16) days; p=0.0149, t-test). In a multiple logistic regression model, male gender and premature rupture of membranes were borderline significant with respect to the occurrence of sepsis - boys had a 4.4-fold risk (OR=0.228 [95% CI: 0.050-1.041]; p=0.0564) and premature rupture of membranes had a 3.5-fold risk (OR=3.462 [0.938-12.779]; p=0.0623). Strong cause variables for the length of stay in the neonatal intensive care unit were birth weight, gestational age and premature rupture of membranes after adjustment. CONCLUSION: The influence of foetal gender on the neonatal outcome in the late preterm group (34 0/7-36 6/7 gestational age) has been relativised.

Individualized correction for maternal weight in calculating the risk of chromosomal abnormalities with first-trimester screening data.

AIM: In the algorithm developed by the Fetal Medicine Foundation (FMF) Germany designed to evaluate the findings of routine first-trimester screening, the false-positive rate (FPR) was determined for the entire study group without stratification by maternal weight. Based on the data received from the continuous audit we were able to identify an increase in the FPR for the weight-related subgroups of patients, particularly for patients with extremely high body weights. The aim of this study was to demonstrate that the variability of the FPR can be reduced through adjusting the concentrations of free ß-HCG and PAPP-A measured in the maternal serum by means of a nonlinear regression function modeling the dependence of these values on maternal weight. MATERIAL AND METHODS: The database used to establish a version of the algorithm enabling control of the FPR over the whole range of maternal weight consisted of n = 123 546 pregnancies resulting in the birth of a child without chromosomal anomalies. The group with positive outcomes covered n = 500 cases of trisomy 21 and n = 159 trisomies 13 or 18. The dependency of the serum parameters free ß-HCG and PAPP-A on maternal weight was analyzed in the sample of negative outcomes by means of nonlinear regression. The fitted regression curve was of exponential form with negative slope. Using this model, all individual measurements were corrected through multiplication with a factor obtained as the ratio of the concentration level predicted by the model to belong to the average maternal body weight of 68.2 kg, over the ordinate of that point on the regression curve which belongs to the weight actually measured. Subsequently, the totality of all values of free ß-HCG and PAPP-A corrected for deviation from average weight were used as input data for carrying out the construction of diagnostic discrimination rules described in our recent paper for a database to which no corrections for over- or under-weight had been applied. This entailed in particular the construction of new reference bands for the corrected biochemical values as the basis for calculating the degree of extremeness (DOE) measures to replace the more traditional MOMs. In the final and most crucial step, stratified FPRs were computed and compared over a set of intervals partitioning the whole range of maternal weight into 18 classes. RESULTS: For the posterior risks of both trisomy 21 and 13 / 18 computed from the weight-corrected database, the use of a cutoff value of 1:150 turned out to be an appropriate choice. For T 21, the overall FPR obtained through comparing the individual risks with this cutoff was found to be 3.51 %. The corresponding proportion of ascertained cases of trisomy 21 detected by means of the new algorithm was 86.2 %. For the trisomy 13 / 18 group, the analogous results were a FPR of 2.07 % and a detection rate (DTR) of 83.0 %, respectively. A comparison between the FPRs obtained for the 18 intervals into which the range of maternal weight had been partitioned, showed the deviation of the strata-specific from the overall FPR to be fairly small: for T 21, the FPR ranged from 2.72 to 4.86 %, and the maximum was found in the group of 87.5 - 95.0 kg. For women with a weight of more than 120 kg, the FPR was only slightly above the FPR for the total sample (3.69 as compared to 3.51 %). Similar results were obtained for the discrimination rule constructed for diagnosing T 13 / 18: here, the minimum FPR (1.17 %) was found for patients weighing more than 120 kg, whereas the maximum (2.66 %) occurred in the interval 75.0 - 77.5 kg. CONCLUSION: In this study we demonstrated that the new algorithm developed by the FMF Germany to estimate risks for fetal trisomies 21 and 13 / 18 combines very good misclassification rates with a far-reaching stability of the false-positive rate against even extreme deviations from the average maternal weight.

Laser coagulation of placental anastomoses with a 30 degrees fetoscope in severe mid-trimester twin-twin transfusion syndrome with anterior placenta.

OBJECTIVE: To assess outcome after fetoscopic laser coagulation (FLC) of placental vascular anastomoses with the 30 degrees fetoscope in mid-trimester severe twin-to-twin transfusion syndrome (TTTS) with completely anterior placenta compared with the regular 0 degrees fetoscope in TTTS with other placental locations. METHODS: This was a prospective study of 176 consecutive monochorionic twin pregnancies undergoing FLC for severe TTTS. Of these, 51 patients required use of the 30 degrees fetoscope (study group) and 125 placental locations permitted use of the 0 degrees fetoscope (controls). RESULTS: The two groups had very similar outcomes. The median gestational age at FLC in the study group vs. control group was 21.0 (range, 17.4-24.6) weeks vs. 20.6 (range, 15.9-24.6) weeks. Both fetuses survived in 58.8% (30/51) of study patients vs. 66.4% (83/125) of controls. At least one fetus survived in 84.3% (43/51) of study patients and 88.8% (111/125) of controls (P = 0.45). Study patients delivered at a median of 34.1 (range, 25.0-38.4) weeks and controls at 34.0 (range, 25.0-40.3) weeks' gestation. CONCLUSIONS: Use of a 30 degrees fetoscope for FLC in cases of technically challenging extensive anterior placentation is associated with an outcome that is very similar to that achieved when a 0 degrees fetoscope is used in cases of more favorable placental location.

A new approach to calculating the risk of chromosomal abnormalities with first-trimester screening data.

PURPOSE: First-trimester screening at 11 - 14 weeks has been proven to be very useful in the early detection of chromosomal defects. The aim of this project was to develop a CE-certified new risk calculation program (PRC = Prenatal Risk Calculation) using a nationwide database. MATERIALS AND METHODS: The database underlying the new risk calculation procedure was established in Germany from 2003 through 2006. Overall, the database includes measurements from 70,030 pregnant women having given birth to healthy children. Following consideration of all pregnancies associated with a chromosomally abnormal outcome, the sample size was 451. The algorithm used for calculating the risk of a chromosomally abnormal outcome comprises the following variables: maternal age, crown-rump length (CRL) (restricted to a range from 45 - 84 mm or, equivalently, 11 + 1 - 14 + 0 weeks of gestation), nuchal translucency (NT), as well as the maternal serum parameters PAPP-A (pregnancy associated plasma protein A) and free beta-hCG (free human chorionic gonadotropin). In a preliminary cross-validation study, we applied both the new algorithm and the FMF UK program to an independent sample containing n = 40,568 pregnancies with negative outcome, n = 187 cases of trisomy 21, n = 34 trisomies 18 and n = 13 trisomies 13. RESULTS: Using the primary sample of 70,030 pregnancies with a negative outcome, reference bands were constructed for the sonographic parameter fetal nuchal translucency and the biochemical parameters PAPP-A and free beta-HCG. Instead of MoM values we used "degree of extremeness" (DoE) values. This statistical parameter has been proven to give more precise results than the MoM measure because it assesses the deviation of the actual measurement value from the centre of the reference band expressed as a multiple of the width of the respective band section. The result of the risk calculation is visualized by means of a traffic light graph which allows the patient to comprehend her individual risk at first glance. The red color indicates a high risk, green a low risk, and yellow represents a moderate risk. In our preliminary cross-validation study the detection rate obtained for the German algorithm was 86.6 % for trisomy 21, 94.1 % for trisomy 18 and 92.4 for trisomy 13. The corresponding detection rates obtained with the same data by the FMF UK program were 86.1 %, 82.3 % and 69.2 % throughout. The false-positive rate was 5.0 % throughout. CONCLUSION: The new risk calculation procedure of the FMF Germany (PRC) has been made available as a CE-certified computer program. In screening for trisomy 21 it yields results comparable to those of the program used by the FMF UK. Regarding the diagnosis of trisomy 13 and 18, even higher detection rates are currently achieved with the German algorithm. Program, data base and license key are available free of charge to registered members of the FMF Germany.

Likelihood of malignancy in breast lesions characterised by ultrasound with a combined diagnostic score.

To determine the positive predictive value of breast ultrasound (US) categories and US features, isolated and in combination, 398 consecutive sonographically diagnosed breast tumours with histologic or cytologic diagnosis were reviewed. Tumour characterisation and the sonographer's diagnoses were recorded prospectively using the diagnostic classification of the European Society of Mastology (EUSOMA) (U2 = probably benign lesion, U3 = an abnormality present of indeterminate significance, U4 = features suspicious of malignancy). In addition, based on the likelihood of malignancy of each US characteristic, a diagnostic score was developed. These two measures were compared. US-guided biopsy revealed 338 benign and 60 (55 invasive and 5 noninvasive) malignant lesions. EUSOMA and diagnostic score classifications did not differ significantly. If all breast tumours classified U3 and U4 were to be tested, every second biopsy (48.3%) would have revealed a carcinoma with a negative predictive value of 99.3%. The frequency of carcinoma in sonographically benign lesions (U2 or score 1) was 0.7 and 2.2%, respectively, an incidence similar to that with mammographic lesions classified as BI-RADS 3 (Breast Imaging Reporting and Data System, probably benign, short interval follow-up suggested). Thus, given that clinical symptoms and real-time imaging influence the sonographer's interpretation, the proposed diagnostic score can improve the diagnostic accuracy of the breast sonogram with the result of reducing invasive testing and maintaining a high detection rate.

Placental vascular anastomoses visualized during fetoscopic laser surgery in severe mid-trimester twin-twin transfusion syndrome.

The aim of this study was to describe the type and number of placental vascular anastomoses identified during fetoscopic laser coagulation in severe mid-trimester twin-twin transfusion syndrome (TTS). In 126 patients with severe TTS, undergoing fetoscopic laser coagulation between 16 and 25 weeks of gestation, the different types of placental anastomoses [arterio-venous (AV), arterio-arterial (AA) and veno-venous (VV)] were counted. In cases of AV anastomoses their direction was identified and four groups were defined: in group 1 there were only anastomoses shunting from donor to recipient. Group 2 consisted of placentae with more anastomoses shunting from donor to recipient than in the opposite direction, group 3 showed an equal number in both directions and in group 4 there were more anastomoses shunting from recipient to donor than in the opposite direction. In 9 cases (7 per cent) the anastomoses could not be clearly identified due to impaired visualization, leaving 117 cases for analysis. The median number of anastomoses found was 5 with a range from 1-14. In all cases AV anastomoses from donor to recipient were present, 36 cases (31 per cent) had also AA anastomoses and 14 cases (12 per cent) showed VV anastomoses. Regarding the direction of AV anastomoses, the results were as follows: there were 35 cases (30 per cent) in group 1, 52 cases (44 per cent) in group 2, 14 cases (12 per cent) in group 3 and 16 cases (14 per cent) in group 4. In 54 (46 per cent) placentae there was at least one thin anastomosis whose type was unclassifiable. There were no placentae showing AV anastomoses only from the recipient to the donor fetus. This study demonstrates that AV anastomoses are the prerequisite for the development of TTS in monochorionic placentae. The majority (74 per cent) of cases showed a higher number of AV anastomoses from donor to recipient than in the opposite direction. In approximately one third of placentae there are also AA anastomoses and the overall number of anastomoses seen and coagulated during fetoscopy is higher than reported in postnatal studies.

Absence of 9q22-9qter in trisomy 9 does not prevent a Dandy-Walker phenotype.

We report on a female fetus with partial trisomy 9 due to a reciprocal translocation in the mother. Routine ultrasound examination at 23 weeks showed hypoplasia of the cerebellar vermis, dilated foramen Magendii, and dilatation of the cisterna magna. Due to the poor prognosis, the parents opted for termination of pregnancy. A postmortem examination confirmed caudal hypoplasia and dysplasia of the cerebellar vermis, resulting in a massively dilated foramen Magendii through which the enlarged cisterna magna communicated with the fourth ventricle. There was also micropolygyria indicating migration disorder. Cytogenetic studies showed a 47,XX,+der(9)t(7;9) (q35;q22.2)mat karyotype. Investigation of the parents revealed a translocation (7;9) (q35;q22.2) in the mother and a normal male karyotype in the father. We systematically searched the chromosome 9 gene map for genes that were trisomic in our fetus and genes that were located on the regions that had the normal two copies of genes. Genes that could potentially be involved in the formation of the Dandy-Walker phenotype are transcription factors or genes responsible for the regulation of normal in particular cerebral development but also adhesion molecules. We conclude that one cause for Dandy-Walker malformation could be a gene dosage effect of genes located on 9pter-9q22. In addition, it seems that absence of trisomy 9 in q22-pter does not prevent abnormal cerebellar development.

The role of ultrasound in female infertility management.

Ultrasound became an important help for the diagnosis of infertility by demonstration of the pelvic organs, of growing ovarian follicles, of intrafollicular structures and of cyclic uterine endometrial changes. Ultrasonic particularities of ovaries and their landmarks such as the ovarian artery, are described. Average ovarian blood flow can be measured. In hormone stimulated cycles, the ultrasonic examination is repeated through ovulation, induction and even afterward. The average diameter of the growing follicle is measured. The results of more than 8000 scans allowed the deduction that ovulation induction would be successful if the preovulatory follicular diameter was between 18 and 24 mm. Where two or more follicles of that diameter are present, multiple pregnancy occurs. The risk of overstimulation can be assessed. The importance of ultrasound is even higher than estradiol because it is impossible to differentiate between one big, some medium or many small follicles with hormone assays. It is possible to see the cumulus oöphorus, but not earlier than 1-2 days before ovulation. Following successful ovulation the mature follicle appears to have a more solid than cystic make-up. Signs of a failure of ovulation are given. Cyclic changes in the histology of the endometrium are described and make it possible to predict ovulation within 12 hr. Ultrasound is an important aid in predicting the time of ovulation more accurately than the basal body temperature and faster and cheaper than hormone profiles. Ultrasound plays a role in egg collection and replacement of the embryo. The detection of ovulation is very important in the treatment of infertility. This was only possible for a longtime by hormone profile. Nowadays ultrasound is an accepted method in the diagnostic procedures of this field. It permits the visualization of the position and size of the uterus, Fallopian tubes and ovaries, the exclusion of genital anomalies and the demonstration of physiological changes of these organs during the menstrual cycle. The main points of ultrasound in the diagnosis of infertility are as follows: Demonstration of the pelvic organs (uterus, Fallopian tube, ovary) and vascular structures. Demonstration of growing ovarian follicles (Measurement of their numbers and sizes). Demonstration of intrafollicular structures (Cumulus oöphorus, Corpus luteum). Demonstration of cyclic uterine endometrial changes. Most of the results were first obtained with high-resolution compound scanners, but the new generation of real-time scanners are equally capable. Sector scanners are superior to linear-array-parallel scanners, especially for the demonstration of specific structural ch

Endoscopic laser coagulation of placental anastomoses in 200 pregnancies with severe mid-trimester twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate perinatal outcome after endoscopic laser coagulation of the placental vascular anastomoses in severe mid trimester twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: In a prospective study between January 1995 and September 1999, we performed laser therapy in 200 consecutive pregnancies with TTTS between 16 and 25 weeks of gestation. We compared outcome of the first group of 73 pregnancies whose outcome has been reported previously in a study comparing laser surgery and serial amniodrainages [Am J Obstet Gynecol 1999;180:717-24], with the following group of 127 patients. RESULTS: The overall survival rate increased from 61% (89/146) in group 1 to 68% (172/254) in group 2. The percentage of pregnancies with survival of both fetuses was 42% (31/73) in group 1 and increased to 54% (69/127) in group 2 (P=0.142). The survival rate for at least one fetus was 81% (103/127) in group 2. The median gestational age at delivery of liveborn babies was 33.7 weeks in group 1 and 34.4 weeks in group 2 with a median interval of 13 weeks between the intervention and delivery. CONCLUSION: This study of a large population of pregnancies with severe second trimester twin-to-twin transfusion syndrome confirms the improvements of outcome after laser therapy as compared to serial amniodrainages reported previously. Furthermore, it shows a trend towards an increase in survival rates with growing experience in this technique, most likely attributable to a more selective identification and efficient coagulation of the placental vascular anastomoses.

[The suitability of high-resolution ultrasound for the detection of DCIS]. / Die Eignung der hochfrequenten Sonografie zur Diagnostik des DCIS.

PURPOSE: Presentation of the suitability of breast ultrasound for detecting DCIS of the breast. MATERIALS AND METHODS: Review of literature on the topic and description of the sonographic features of DCIS illustrated by cases. RESULTS: Breast ultrasound is currently capable of detecting DCIS with a comparable success rate to that of mammography. The advantages of sonography become obvious in cases of DCIS without microcalcifications and DCIS in dense or very dense breasts. The assessment of the sonographic architecture of the whole lobe, not just circumscribed lesions, is becoming increasingly important. CONCLUSION: Breast ultrasound represents an important tool for detecting DCIS in addition to mammography.