[S3 guidelines on "full-term vaginal birth" from an anesthesiological perspective : Worthwhile knowledge for anesthesiologists]. / S3-Leitlinie "Vaginale Geburt am Termin" aus anästhesiologischer Sicht : Wissenswertes für den Anästhesisten.

The publication of the new S3 guidelines on "full-term vaginal birth" and the guidelines on cesarean section, also published in 2020, provide further steps towards the promotion of evidence-based medicine in obstetrics, even if the exact configuration of neonatal monitoring during birth, in particular, is still the subject of current discussions. The multiprofessionality in the medical supervision of a birth is also fundamentally well-represented in the compilation of the S3 guidelines by the participating actors and specialist societies. Important from an anesthesiological perspective is the fact that neuraxial procedures still represent the gold standard in obstetric analgesia. With remifentanil PCA an alternative option is available that enables a reliable analgesia to be accomplished, e.g. when there are contraindications to performing neuraxial methods, if this is appropriate under the prevailing circumstances (1:1 support and appropriate monitoring). During an uncomplicated birth the strict fasting rules are relaxed. Overall, the guidelines underline the importance of self-determination and self-control for the expectant mother and give the highest priority to the safety and well-being of mother and child; however, this presupposes that the expectant mother is sufficiently informed about the value of neuraxial analgesia. For this it appears to be of importance to initiate information proposals, which go beyond the usual information sessions for parents that are often organized exclusively by midwives.

Role of vitamin D in cell-cell interaction of fetal endothelial progenitor cells and umbilical cord endothelial cells in a preeclampsia-like model.

Maternal endothelial dysfunction is a cental feature of preeclampsia (PE), a hypertensive disorder of pregnancy. Factors in the maternal circulation are thought to contribute to this endothelial dysfunction. Although understudied, factors in the fetal circulation may influence fetal endothelial cell interactions with endothelial progenitor cells as critical steps in placental angiogenesis. We hypothesize that cell-cell interactions that are important for pregnancy health are impaired by fetal serum from PE pregnancies and that 1,25(OH)2-vitamin D3 attenuates the negative effects of this serum on cell function. We tested the ability of fetal cord blood-derived endothelial progenitor cells [endothelial colony-forming cells (ECFCs)] to invade into established monolayers and capillary tubule-like structures of human fetal umbilical venous endothelial cells (HUVECs), while in the presence/absence of fetal cord serum from uncomplicated or PE pregnancies, and tested the ability of 1,25(OH)2-vitamin D3 to modulate the serum-mediated effects. PE cord serum reduced the invasion of fetal ECFCs into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. PE cord serum reduces the ability of fetal endothelial progenitor cells to incorporate into fetal endothelial cell networks. Physiologic concentrations of vitamin D reverse these PE serum-mediated effects. These data appear consistent with lines of evidence that vitamin D has antipreeclampsia effects.

The microstructure in the placenta is influenced by the functional diversity of HLA-G allelic variants.

The main expression sites of HLA-G are human extravillous trophoblast cells. The interaction of HLA-G with uterine NK cells promotes their maturation and differentiation into decidual NK (dNK) cells. dNK cells secrete chemokines, cytokines, and proangiogenic factors in favor of a vascular remodeling and an immune suppressive microenvironment of the decidua. HLA-G is the most polymorphic member of the oligomorphic non-classical HLA molecule family; yet, the impact of polymorphic differences is not comprehensively understood. sHLA-G levels in embryo culture medium correlate with successful pregnancy; however, it remains questionable if HLA-G allelic diversity impacts on the outcome of dNK cell development. We utilized synthetic sHLA-G*01:01, 01:03, and 01:04 molecules and transduced K652/mHLA-G*01:01, 01:03, and 01:04 cells to study the biological interaction between HLA-G alleles and primary NK cells of human term placenta. Despite its low frequency, HLA-G*01:04 and not the most prevalent allele HLA-G*01:01 appear to be strong catalysts of dNK cell proliferation. Concluding, this study illustrates novel insights into the impact and binding efficiency of the three most common variants of HLA-G on primary placental NK cells.

[Pathoanatomical and clinical aspects of the placenta in preterm birth]. / Pathologisch-anatomische und klinische Aspekte der Plazenta bei Frühgeburt.

BACKGROUND: Prematurely born children show a clearly elevated risk for perinatal morbidity, long-term pediatric morbidities and development of chronic diseases in adulthood compared to babies born at term. The pathoanatomical investigation of placentas from preterm births is useful for assessing the etiology, the risk of recurrence and the prognosis for the child. AIMS: The focus is on presenting the clinical and pathoanatomical characteristics of acute chorioamnionitis as a frequent cause of preterm induction of labor and pregnancy-induced hypertension, in particular preeclampsia as a frequent reason for elective cesarean section. Other lesions, sometimes of unclear etiology associated with preterm birth and substantially elevated risk of recurrence are reviewed. The clinical correlations and therapeutic options of the various diseases are discussed taking the risk of recurrence into consideration. MATERIAL AND METHODS: Examination of placentas, association with the clinical course and a literature search. RESULTS AND DISCUSSION: Acute chorioamnionitis and omphalovasculitis can be histologically subdivided into different stages which correlate with the clinical severity and the prognosis for the newborn child. Chronic deciduitis, chronic chorioamnionitis, villitis of unknown etiology, massive perivillous fibrin deposition and chronic histiocytic intervillositis are entities of unclear etiology associated with recurrent abortion and preterm birth. Autoimmune diseases and thrombophilia are occasionally associated with these pathologically defined lesions. Pregnancy-associated hypertensive disease and particularly preeclampsia as the cause of intrauterine developmental delay and elective cesarean section often show characteristic pathoanatomical placental lesions, which can give indications for the severity and duration of the disease and the prognosis for the child. Early onset (<34 weeks of gestation) and late onset preeclampsia show clinical and morphological differences. Subsequent pregnancies are classified as being at risk and screening for preeclampsia should be clinically performed.

Quality Requirements for the early Fetal Ultrasound Assessment at 11-13+6 Weeks of Gestation (DEGUM Levels II and III).

The early fetal ultrasound assessment at 11 - 13(+6) weeks of gestation remains the cornerstone of care despite the progress in diagnosing fetal chromosomal defects using cell-free fetal DNA (cffDNA) from the maternal circulation. The measurement of nuchal translucency (NT) allows the risk calculation for the fetal trisomies 21, 18 and 13 but also gives information on those fetal chromosomal defects which are at present unable to be detected using cffDNA. Nuchal translucency is the only auditable parameter at 11 - 13(+6) weeks and gives thus information on the quality of the first trimester anomaly scan. In addition it gives indirect information on the risks for fetal defects and for cardiac anomalies. Also the chances for a healthy live baby can be estimated. As experience with first trimester anomaly scanning increases, and the resolution of the ultrasound equipment has increased substantially, more and more details of the fetal anatomy become accessible at the first trimester scan. Therefore fetal anatomical defects and complex anomalies have become amenable to examination in the first trimester. This guideline describes compulsory and optional parameters for investigation at the first trimester scan and outlines a structured method of examining a first trimester fetus at 11 - 13(+6) weeks of gestation.

Background Knowledge and Attitude of Pregnant Women towards Ultrasound Screening at 20-23 Weeks Gestation.

BACKGROUND: Prenatal ultrasound screening in the second trimester is widely used in maternal health care. Prenatal diagnosis and prenatal screening is often exposed to several accusation, such as inducing unnecessary anxiety, carrying out a selection and forcing pregnant women into attending ultrasound screening. The aim of this study was to investigate the knowledge and the intention of pregnant women attending the second trimester ultrasound screening. PATIENTS AND METHODS: This was a prospective study. Women attending the 20 weeks anomaly scan were given an anonymous questionnaire to evaluate the background knowledge about the anomaly scan and their opinion about prenatal screening. RESULTS: 600 (96.7%) of 620 recruited women filled in the questionnaire completely. To the majority (>80%) of women it is important to exclude severe fetal anomalies and to secure normal fetal growth. The background knowledge of the women was good, but a clear supply of information and a detail counselling would improve the understanding, especially in the group of lower education. The majority of the women stated that the 20 weeks anomaly scan should be offered to every woman. CONCLUSION: Prenatal ultrasound examination is not only essential from a medical point of view for example for important information regarding the status of the fetus, but also has a major impact as a positive psychological factor for pregnant women.

Cranial and cerebral signs in the diagnosis of spina bifida between 18 and 22 weeks of gestation: a German multicentre study.

OBJECTIVE: The aim of this article is to study secondary cranial signs in fetuses with spina bifida in a precisely defined screening period between 18 + 0 and 22 + 0 weeks of gestation. METHOD: On the basis of retrospective analysis of 627 fetuses with spina bifida, the value of indirect cranial and cerebral markers was assessed by well-trained ultrasonographers in 13 different prenatal centres in accordance with the ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) guidelines on fetal neurosonography. RESULTS: Open spina bifida was diagnosed in 98.9% of cases whereas 1.1% was closed spina bifida. Associated chromosomal abnormalities were found in 6.2%. The banana and lemon signs were evident in 97.1% and 88.6% of cases. Obliteration of the cisterna magna was seen in 96.7%. Cerebellar diameter, head circumference and biparietal diameter were below the 5th percentile in chromosomally normal fetuses in 72.5%, 69.7% and 52%, respectively. The width of the posterior horn of the lateral ventricle was above the 95th percentile in 57.7%. The secondary cranial and cerebral signs were dependent on fetal chromosome status and width of the posterior horn. Biparietal diameter was also dependent on the chromosome status with statistical significance p = 0.0068. Pregnancy was terminated in 89.6% of cases. CONCLUSION: In standard measuring planes, lemon sign, banana sign and an inability to image the cistern magna are very reliable indirect ultrasound markers of spina bifida. © 2014 John Wiley & Sons, Ltd.

[Evaluation of intrauterine death: importance of examination of fetal, placental and maternal factors]. / Evaluierung des intrauterinen Fruchttods: Stellenwert der Untersuchung fetaler, plazentarer und maternaler Faktoren.

AIMS: Intrauterine death is a multifactorial major complication during pregnancy. In this retrospective analysis the pathological anatomical findings of fetuses and placentas as well as maternal factors were evaluated. MATERIAL AND METHODS: A retrospective screening of post-mortem examinations, corresponding placental examinations and clinical data on maternal status (1998-2008) was carried out. A classification of all findings was made with the ReCoDe system and induced abortions and cases with incomplete data were excluded from the study. RESULTS: A total of 84 pregnancies involving 87 fetuses (9 siblings) were evaluated. The median gestation age was 20 weeks (range 12-41). The evaluation based on the ReCoDe system revealed that intrauterine death was mainly associated with placental diseases (n = 63) and to a lesser extent with fetal malformations (n = 15) or maternal diseases (n = 4). Idiopathic cases were rare (n = 2). CONCLUSIONS: Placental examination is important for explaining intrauterine death because in most cases an association with placental diseases can be found but fetal malformation and maternal diseases must be taken into account.

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.

Analysis of the impact of PAPP-A, free ß-hCG and nuchal translucency thickness on the advanced first trimester screening.

OBJECTIVES: The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free ß-hCG used in combined first trimester screening and to determine their contribution in the risk assessment. METHODS: A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC). RESULTS: Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free ß-hCG showed the lowest AUC. Combining PAPP-A and free ß-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters. DISCUSSION: A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free ß-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-ß-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics.

Characterisation of the learning curve of caesarean section.

INTRODUCTION: Caesarean section is one of the common operations in medicine. As almost all interventions, the quality of the operation depends on the training and skills of the surgeon. This study aims at characterising the learning curve of caesarean section. MATERIAL AND METHODS: All patients with a singleton pregnancy who underwent a caesarean section between 2000 and 2009 in our university hospital were identified. We analysed datasets from beginners (no experience at all) and experienced surgeons (>300 caesarean sections, consultant) comparing the parameter incision-suture time (I-S time), incision-delivery time (I-D time), maternal blood loss, umbilical artery pH (ua-pH), APGAR score after 1, 5 and 10 min, mean time in hospital and postoperative complications. In addition, the first 100 caesarean sections of each beginner surgeon were divided in groups of 10 (1-10, 11-20, etc.) and analysed using the above-mentioned parameters. The learning curves were calculated. RESULTS: 2,515 of 3,844 operations were carried out by 23 experienced surgeons versus 1,329 operations by 22 beginners. The I-S time and I-D time was significantly higher in the beginners group than in the experienced surgeon's group (45.9 vs. 41.3 min, p < 0.001). Furthermore, for the first ten caesarean sections, the mean I-S time (47.9 min, 95% CI 45.7-50.0 min vs. 31-40th caesarean section with 43.1 min, 95% CI 40.9-45.3 min, p < 0.0001) and I-D time (9.5 min, 95% CI 8.6-10.5 min vs. 71-80th caesarean section with 4.8 min, 95% CI 4.2-5.4 min, p < 0.0001) was significantly higher than of the subsequent datasets of ten operations, showing a typical learning curve. CONCLUSION: The learning curve for the total operation time and incision-delivery time reaches a flatter part after 10-15 caesarean sections. However, the learning process is highly individualised and difficult to predict, so that supervision and evaluation of the trainee by an experienced surgeon is important.

Pitfalls of ultrasonographic yolk sac measurement.

PURPOSE: Novel aneuploidy screening has been suggested for measuring the yolk sac during very early pregnancy. However, in a pilot study the measured diameters differed up to 29 % from the overall average. The aim of this study was to analyze the impact of image magnification on yolk sac measurement. MATERIALS AND METHODS: From November 3, 2009 to July 28, 2010, 119 yolk sac measurements were performed. During each examination, each yolk sac was examined once with standard image magnification and once by live scan zoom. RESULTS: The measurement values were 5 % smaller in the standard image. The mean relative ratio (RR), median RR, and standard deviation (SD) were 0.951, 0.950, and 0.103 mm, respectively (95 % CI 0.744 to 1.158 mm). Regarding absolute differences, the mean, median, and standard deviation were -0.222 mm, -0.220 mm, and 0.473 mm, respectively, (95 % CI -1.169 to + 0.725 mm). With standard zoom (magnified images), the SD was 1.142 mm (1.099 mm). CONCLUSION: Five criteria should be regarded for optimal image settings: image magnification during live scan, optimal gain setting, enhanced gamma level, median section plane, and out-to-out caliper placement.

Lymphatic capillary hypoplasia in the skin of fetuses with increased nuchal translucency and Turner's syndrome: comparison with trisomies and controls.

Fetuses with Turner's syndrome or trisomies 21, 18 and 13 show excess of skin, which can be visualized by ultrasonography as increased nuchal translucency at 11-13(+6) weeks' gestation. The objective of this study was to gain insight in the development and distribution of blood vessels, lymphatic capillaries of the cutis and lymphatic collectors of the cutis and subcutis and to study developmental changes with increasing gestation. Immunofluorescence of cryosections with 10 specific antibodies was used to investigate the nuchal skin of three fetuses with Turner syndrome's and to differentiate lymphatics, lymph capillaries (FLT4, PTN 63, LYVE1, PROX1), blood vessels (KDR, CD 31, PDPN), blood clotting activity (von Willebrand factor), basement membranes and big vessels (Laminin, Collagen Type IV). The findings were compared with those in seven fetuses with trisomy 21 and two fetuses each with trisomies 18 or 13, respectively, as well as six normal controls. Immunoreactive receptors for vascular endothelial growth factors (FLT4) were decreased in lymphatic capillaries of the skin of Turner fetuses. Accordingly, LYVE1 was scarce and PROX1 staining was less intense in the dermis of Turner fetuses. Lymphatic collectors were, however, evenly stained. In normal fetuses and in those with trisomies, lymphatic capillaries were evenly distributed. We conclude that lymphatic capillary hypoplasia might be responsible for nuchal cystic hygroma in Turner syndrome. The biological basis for increased nuchal translucency in trisomies may however be different.

First-trimester placental growth factor as a marker for hypertensive disorders and SGA.

OBJECTIVE: The objective of this study was to examine first-trimester maternal serum placental growth factor (PlGF) levels in pregnancies which later develop hypertensive and growth complications. METHODS: In this case-control study, PlGF levels were measured by AutoDELFIA immunoassay platform. There were 47 cases of at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age (SGA), haemolysis elevated liver enzymes and low platelets (HELLP) and gestational hypertension (GH) and 452 matched controls. RESULTS: PlGF levels were significantly lower in cases of all PE, early PE, HELLP, all SGA, early SGA and SGA without PE, but not in GH, late PE, late SGA, PE with SGA or PE without SGA or HELLP. CONCLUSION: Low levels of first-trimester PlGF provide a good indicator of SGA complications and some hypertensive disorders, in particular severe cases of PE such as early onset and HELLP syndrome.

A mixture model of nuchal translucency thickness in screening for chromosomal defects: validation of a single operator dataset.

OBJECTIVE: (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach. METHODS: Database query, viable singletons [crown-rump length (CRL) 45-84 mm corresponding to 11-13(+6) weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied. RESULTS: Seventy-four of 4171 were lost to follow-up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log-transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta-NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false-positive rate (FPR), the trisomy 21 detection rate was 83%. CONCLUSIONS: The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated.

Maternal serum ADAM-12 as a potential marker for different adverse pregnancy outcomes.

OBJECTIVE: To investigate first-trimester ADAM-12 levels in pregnancies which later develop hypertensive and growth complications. METHODS: First-trimester serum samples (11(+0) to 13(+6) weeks) were retrieved from frozen storage. 47 samples with at least one of the following adverse outcomes: pre-eclampsia (PE), small for gestational age, HELLP syndrome and gestational hypertension were analysed and 452 controls matched to the cases by gestational age and length of storage were analysed. ADAM-12 levels were measured by the automated AutoDELFIA immunoassay platform. RESULTS: ADAM-12 was found to increase with gestational age (11(+0) to 13(+6) weeks) and decrease with increasing maternal weight and in women who smoked. After correction, ADAM-12 median multiples of the median were increased in cases with HELLP syndrome, all PE and PE only. CONCLUSION: The increased first-trimester levels of ADAM-12 in PE and HELLP are in contrast with previous findings. The usefulness of ADAM-12 as a marker for adverse outcomes is still unclear.