Maternal sepsis in the era of genomic medicine.

PURPOSE: Maternal sepsis remains one of the leading causes of direct and indirect maternal mortality both in high- and low-income environments. In the last two decades, systems biology approaches, based on '-omics' technologies, have started revolutionizing the diagnosis and management of the septic syndrome. The scope of this narrative review is to present an overview of the basic '-omics' technologies, exemplified by cases relevant to maternal sepsis. METHODS: Narrative review of the new '-omics' technologies based on a detailed review of the literature. RESULTS: After presenting the main 'omics' technologies, we discuss their limitations and the need for integrated approaches that encompass research efforts across multiple '-omics' layers in the '-omics' cascade between the genome and the phenome. CONCLUSIONS: Systems biology approaches are revolutionizing the research landscape in maternal sepsis. There is a need for increased awareness, from the side of health practitioners, as a requirement for the effective implementation of the new technologies in the research and clinical practice in maternal sepsis.

[Transcervical Embryoscopy after Missed Abortion in Monoamniotic Twins with Discordant Exencephaly]. / Transzervikale Embryoskopie nach verhaltenem Abort in monoamnioten Zwillingen mit diskordanter Exenzephalie.

INTRODUCTION: Monoamniotic twins are considered a cause of high-risk pregnancies. Thereby, discordant malformations do occur rarely. A discordant exencephaly has been described in only a few cases. Transcervical embryoscopy can be performed in cases of monoamniotic twins with missed abortion directly before the abort-curettage. CASE REPORT: The case of a 35-year-old G1/P0 women in the 12(th) week of pregnancy is described. She had a monoamniotic twin pregnancy with discordant exencephaly and missed abortion diagnosed at 11+2 weeks. A transcervical embryoscopy was performed immediately before the abort-curettage and identified the discordant exencephaly and an additional umbilical cord knot of the 2 foetuses as a probable cause for the abortion. DISCUSSION: The transcervical embryoscopy lead in our case report to the diagnosis of a umbilical cord knot in a monoamniotic twin pregnancy with missed abortion. We also identified a discordant exencephaly by embryoscopy. With blunt access to the amniotic cavity, the transcervical embryoscopy applies only a minor additional risk to the abort-curettage. However, it should only be performed when the patient explicitly asks for enhanced diagnostics. CONCLUSION: Transcervical embryoscopy can be performed as an additional diagnostic tool in cases of monoamniotic twins with missed abortion. However, a detailed risk-benefit analysis should be done upfront in consultation with the patient.

[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.

[Fetal neurosonography using 3-dimensional multiplanar sonography]. / Fetale Neurosonografie mittels 3-dimensionaler multiplanarer Sonografie.

This review focuses on the examination of the fetal brain, using three-dimensional (3D) ultrasound and the multiplanar rendering mode (MPR). The routine examination of the brain is achieved with axial planes but a dedicated fetal neurosonogram requires additional coronal and sagittal views, in order to provide a complete view of the different brain structures. Because these planes are difficult to obtain under many conditions, the present paper shows how 3D MPR allows one to obtain 1 or multiple reconstructed images from a digital volume. The display can be either as orthogonal planes, tomographic planes with parallel slices or as one single plane of the region of interest, which can be selected by the examiner. This approach allows easily the demonstration of the corpus callosum, the cerebellar vermis, the three-horn view, the foetal hippocampus and other regions. In addition, early neurosonography of the developing brain from the 7th week of pregnancy onwards can be achieved.

[Nausea and vomiting as evolutionary mechanisms of the complex adaptation reaction to pregnancy]. / Ubelkeit und Erbrechen als evolutionäre Mechanismen der vielschichtigen Anpassungsreaktion an die Schwangerschaft.

INTRODUCTION: Nausea and vomiting during pregnancy (NVP) constitute a frequent and often highly unpleasant syndrome during the sensitive period of early pregnancy, which has been intensively investigated. However, many questions remain unanswered, particularly the counterintuitive association with a better pregnancy outcome. Under these circumstances our functional concept to interpret NVP as an evolutionary mechanism of complex adaptation to early pregnancy seems promising. METHOD: In this cross-cultural study data were collected from 565 mothers, who had given birth recently in South Africa, Guatemala and Germany, using a standardised questionnaire interview. RESULTS: There was a cross-culturally similar prevalence and clinical presentation of NVP, showing a high degree of subjective suffering. We found evidence supporting a multifactoral aetiology of biological, psychological and sociological factors. Likewise, NVP seems to have multiple effects, concerning nutrition, behaviour, perception, psychology and social support. DISCUSSION AND CONCLUSION: Our new and previously existing data support the idea that NVP has been selected for by evolution, as a functional adaptation to vulnerable early pregnancy, which benefits mother and child. This assumption is supported by the correlation of NVP with a better foetal prognosis, the cross-culturally high prevalence and a favorable relation of low biological costs versus high effects. The benefit of NVP could be realised by nutritional change, increased social support, more passive and careful behaviour, earlier recognition of pregnancy and a positive influence on foetal development. To understand the functionality of NVP, one needs to consider the complex somato-psychoemotional interplay in the context of an environment of evolutionary adaptedness (EEA).

Extended hyperemesis gravidarum in a patient after total thyroidectomy.

INTRODUCTION: Human chorionic gonadotropin is regarded as, at least, one of the main factors responsible for hyperemesis gravidarum by direct stimulation of the thyroid gland on the basis of a close homology to the structure of TSH. However, questions to this theory of hCG-induced gestational hyperthyroidism still remain. CASE REPORT: We present for the first time a rare case of hyperemesis gravidarum in a patient with a previous removed thyroid gland and an adequate thyroxin replacement. In this case report we present an extended hyperemesis gravidarum in a patient after total thyroidectomy and thus artificially well-set thyroid parameters. CONCLUSION: Although transient hyperthyroidism is widely thought to be causative of a hyperemesis during pregnancy, this case report with a mildly hypothyroidism emphasizes that there might be other, yet unknown, factors that can cause such a severe complication.

[Fetal programming: prevention of perinatal acquired predispositions of diseases in later life]. / Fetale Programmierung: Prävention von perinatal erworbenen Gesundheitsrisiken.

Alterations of the metabolic and hormonal environment of the fetus may cause predispositions to the development of disorders and diseases in later life. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes. Elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism. Diagnosis and therapy of gestational diabetes in time may prevent metabolic and cardiovascular diseases in later life. This concept has new important implications for chances and challenges of perinatal preventive medicine in the future.

Expression of inhibin/activin subunits alpha (-alpha), betaA (-betaA), and betaB (-betaB) in placental tissue of normal, preeclamptic, and HELLP pregnancies.

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-alpha- and both beta-subunits (betaA-and betaB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-alpha subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-betaB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-betaA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-alpha and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower betaB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the betaA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function.

Expression of inhibin/activin subunits alpha (-alpha), beta A (-beta (A)) and beta B (-beta (B)) in placental tissue of normal and intrauterine growth restricted (IUGR) pregnancies.

During human pregnancy the placenta produces a variety of proteins like steroid hormones and their receptors that are responsible for the establishment and ongoing of the feto-placental unit. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (beta (A) or beta (B)). Aims of the present study were the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with fetal growth restriction (IUGR). Slides of paraffin embedded placental tissue were obtained after delivery from patients diagnosed with IUGR (n = 6) and normal term placentas (n = 8). Tissue samples were fixed and incubated with monoclonal antibodies inhibin/activin-subunits -alpha, -beta (A), -beta (B). Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score and statistical analysis was performed (P<0.05). A significant lower expression of the inhibin-alpha subunit in IUGR extravillous trophoblast compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytiotrophoblast. Additionally, a significant down-regulation of inhibin-beta (B) subunit in extravillous trophoblast cells in IUGR syncytiotrophoblast cells was demonstrated. A co-localisation of inhibin-alpha and the beta-subunits was also observed, suggesting a production and secretion of intact inhibin A and inhibin B. Although the precise role of these inhibin/activin subunits in human placenta and IUGR pregnancies is still unclear, they could be involved in autocrine/paracrine signalling, contributing to several aspects like angiogenesis and tissue remodelling.

Prenatal constriction of the fetal ductus arteriosus--related to maternal pain medication?

Physiological fetal circulation requires patency of the ductus arteriosus. As gestation proceeds, the sensitivity of the ductus to dilating prostaglandins diminishes. The sensitivity to constricting agents like PGE-synthetase inhibitors, present in many analgetics, however, increases. Fetuses affected by an antenatal constriction of the ductus arteriosus (DC) may present with different signs of cardiac failure including dilated right ventricle, tricuspid regurgitation and abnormal venous Doppler. We report on four cases with prenatal DC, presenting at 34, 35, 36 and 37 weeks of gestation. They were referred to fetal echocardiography because of abnormal routine echo scans with unexplained signs of right heart decompensation. Three patients were medicated during pregnancy with either aspirin (low dose), metamizole or ibuprofen. One patient did not take any drugs, especially no pain medication drug in pregnancy. Immediate delivery was performed in all cases. The neonates were in a good condition; echocardiography showed different degrees of right heart hypertrophy which disappeared in all infants by the age of 3 months except in case 2. Unexplained fetal right heart decompensation requires detailed echocardiographic evaluation of the ductus arteriosus and a sophisticated medical history with regard to analgesics. In contrast to ibuprofen and high-dose aspirin, metamizole and low-dose aspirin have not yet been reported as possible agents constricting the fetal arterial duct. In any suspected context, early delivery as in our cases may save babies life. Any application of non-steroidal anti-inflammatory drugs in pregnancy requires close fetal follow-up due to their potentially life-threatening effect.

Obstetrical parameters influencing the duration of the second stage of labor.

OBJECTIVE: To investigate the impact of parameters influencing the duration of the second stage of labor in vaginal deliveries. STUDY DESIGN: 1200 consecutive vaginal deliveries were analyzed. Descriptive statistics are reported for parity, duration of first and second stage of labor, maternal age, birth weight, position of the fetal head, epidural analgesia and oxytocin augmentation. Logistic regression analysis was performed to assess the contribution of different variables to the length of the second stage of labor. RESULTS: The mean length of the second stage was 70 min. In univariate analysis, parity, oxytocin augmentation and epidural analgesia, as well as occipito-posterior presentation were significant parameters associated with a prolonged second stage of labor. No correlation was found for birth weight and maternal age. In multivariate regression analysis, nulliparity and epidural analgesia were the strongest risk factors for a prolonged second stage. CONCLUSIONS: The impact of epidural analgesia on the second stage of labor should be considered in obstetrical management.