DEGUM Recommendations on Diagnostic Puncture in Prenatal Medicine. / Empfehlungen der DEGUM zu diagnostischen Punktionen in der Pränatalmedizin.

Diagnostic puncture (amniocentesis, chorionic villus sampling, and fetal blood sampling) is an essential part of prenatal diagnostics and the only established and sufficiently scientifically evaluated possibility of diagnosing genetic diseases from pregnancy-specific cells. The number of diagnostic punctures in Germany, as in other countries, has fallen significantly. This is largely due to the introduction of first-trimester screening with further detailed ultrasound examination of the fetus and the analysis of cf-DNA (cell-free DNA) from maternal blood (noninvasive prenatal test - NIPT). On the other hand, knowledge about the incidence and appearance of genetic diseases has increased. The development of modern molecular genetic techniques (microarray and exome analysis) makes a differentiated investigation of these diseases increasingly possible. The requirements for education and counseling regarding these complex correlations have thus increased. The studies performed in recent years make it clear that diagnostic puncture performed in expert centers is associated with a low risk of complications. In particular, the procedure-related miscarriage risk hardly differs from the background risk for spontaneous abortion. In 2013, the Section of Gynecology and Obstetrics of the German Society for Ultrasound in Medicine (DEGUM) published recommendations on diagnostic puncture in prenatal medicine 1. The developments described above and new findings in recent years make it necessary to revise and reformulate these recommendations. The aim of this review is to compile important and current facts regarding prenatal medical puncture (including technique, complications, genetic examinations). It is intended to provide basic, comprehensive, and up-to-date information on diagnostic puncture in prenatal medicine. It replaces the publication from 2013 1.

The role of ultrasound in first-trimester screening after the introduction of NIPT as a service of public health insurance - a consensus statement of the Fetal Medicine Foundation (FMF) Germany.

Combined first-trimester screening (FTS) and noninvasive prenatal testing (NIPT) have been proven to be reliable noninvasive procedures to detect the most common chromosomal abnormalities (trisomies 21, 18, 13) in the first trimester. The aim of this paper is to demonstrate the strengths and limitations of these two procedures and to give a consensus statement of the Fetal Medicine Foundation (FMF) Germany on how to use the two techniques in the first trimester after the introduction of NIPT as a service of the statutory health insurance companies in Germany.

Basic Gynecologic Ultrasound Examination (Level I): DEGUM, ÖGUM, and SGUM Recommendations. / Qualitätsanforderungen an gynäkologische Ultraschall-Untersuchungen der DEGUM-Stufe I: Empfehlungen der DEGUM, ÖGUM und SGUM.

Ultrasound has become an essential diagnostic tool in gynecology, and every practicing gynecologist must be able to differentiate normal from pathologic findings, such as benign or malignant pelvic masses, adnexal torsion, pelvic inflammation disease, endometriosis, ectopic pregnancies, and congenital uterine malformations at least on a basic level. A standardized approach to the correct settings of the ultrasound system, the indications for gynecologic ultrasound investigations, and the sonographic appearance of normal anatomy and common pathologic findings in the standard planes are important prerequisites for safe and confident clinical management of gynecologic patients. Based on current publications and different national and international guidelines, updated DEGUM, ÖGUM, and SGUM recommendations for the performance of basic gynecologic ultrasound examinations were established.

Quality Requirements for gynecological ultrasound examinations of DEGUM level II - Recommendations of the Sections/Working Groups Gynecology and Obstetrics of DEGUM, ÖGUM and SGUM. / Qualitätsanforderungen an die gynäkologischen Ultraschalluntersuchungen der DEGUM Stufe II ­ Empfehlungen der Sektionen/Arbeitskreise Gynäkologie und Geburtshilfe der DEGUM, ÖGUM und SGUM.

Gynecological sonography is the central and most frequently used technical examination method used by gynecologists. Its focus is on the clarification of masses of the uterus and the adnexa, fertility diagnosis, clarification of bleeding disorders and chronic and acute pelvic problems, pelvic floor and incontinence diagnosis as well as the differential diagnosis of disturbed early pregnancy. The indication for diagnostic and therapeutic interventions, preoperative planning and postoperative controls are largely based on the findings of gynecological sonography. These examinations are particularly dependent on the experience of the examiner.Based on the proven multi-stage concept of obstetric diagnostics, gynecological sonography should primarily be performed by an experienced and specialized examiner in patients for whom the initial gynecological examinations have not yet led to a sufficient assessment of the findings. So that the expert status required for this has an objective basis, the Gynecology and Obstetrics Section of DEGUM in cooperation with ÖGUM and SGUM implemented the option of acquiring DEGUM Level II for gynecological sonography. The effectiveness of the care in the multi-level concept depends on the quality of the ultrasound examination at level I. Quality requirements for the basic examination and the differentiation between the basic and further examination have therefore already been defined by DEGUM/ÖGUM. The present work is intended to set out quality requirements for gynecological sonography of DEGUM level II and for the correspondingly certified gynecologists.Common pathologies from gynecological sonography and requirements for imaging and documentation are described.

Doppler ultrasound in pregnancy - quality requirements of DEGUM and clinical application (part 2). / Dopplersonografie in der Schwangerschaft ­ Qualitätsanforderungen der DEGUM und klinischer Einsatz (Teil 2).

This second part on Doppler sonography in prenatal medicine and obstetrics reviews its clinical applications. While this has not become the initially anticipated screening tool, it is used for the diagnosis and surveillance of a variety of fetal pathologies. For example, the sonography-based determination of uterine artery blood flow indices is an important parameter for the first trimester multimodal preeclampsia risk assessment, increasing accuracy and providing indication for the prophylactic treatment with aspirin. It also has significant implications for the diagnosis and surveillance of growth-restricted fetuses in the second and third trimesters through Doppler-sonographic analysis of umbilical artery, middle cerebral artery and ductus venosus. Here, especially the hemodynamics of the ductus venosus provides a critical criterium for birth management of severe, early-onset FGR before 34 + 0 weeks of gestation. Further, determination of maximum blood flow velocity of the middle cerebral artery is a central parameter in fetal diagnosis of anemia which has been significantly improved by this analysis. However, it is important to note that the mentioned improvements can only be achieved through highest methodological quality. Importantly, all these analyses are also applied to twins and higher order multiples. Here, for the differential diagnosis of specific complications such as TTTS, TAPS and TRAP, the application of Doppler sonography has become indispensable. To conclude, the successful application of Doppler sonography requires both exact methodology and precise pathophysiological interpretation of the data.

Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany.

BACKGROUND AND AIMS: Prevalence data of hepatitis B virus (HBV) in pregnant women in the Eastern part of Germany are missing. More importantly, no data on HBV's impact on pregnancy is known in patients living in the Western hemisphere. Our aim was to assess the prevalence of hepatitis B surface antigen (HBsAg) and its impact on pregnancy in women admitted to the department of gynecology at a German university hospital. PATIENTS AND METHODS: 8,193 women who delivered at the university hospital between 2001 and 2006 were retrospectively screened for HBsAg and if positive investigated for pregnancy and newborn complications in comparison to women without hepatitis B infection. RESULTS: 39 (0.48%) women were found to be HBsAg carriers, which is in line with other data showing lower rates in Eastern parts of Germany in relation to the Western part. Furthermore, prevalence was much lower in German-born women (0.2%) in comparison to Asian-born women (9.1%). Secondly, women with HBsAg had no significantly increased prevalence of adverse pregnancy outcomes. CONCLUSION: There is a low prevalence of HBV infection, especially among German-born women. There is no significant evidence to support increased complications in relation to HBV infection in our study.

Prenatal and Obstetric Parameters of Late Terminations: A Retrospective Analysis.

Background In Germany, the highly sensitive issue of late terminations of pregnancy and feticide is regulated in Sec. 218a para. 2 of the German Penal Code (medical indication). This study aimed to investigate the prenatal obstetric approach after feticide and the rate of maternal complications. Material and Methods All feticides of singleton pregnancies carried out at Leipzig University Hospital (n = 164) in the period between 01/2016 and 12/2019 were retrospectively analyzed. Selective feticides of multiple pregnancies were excluded from the study. Target indicators for the prenatal obstetric approach were sonographic accuracy of estimation, method used to induce feticide, time between feticide and delivery, and whether curettage was required. The rate of maternal complications was defined as blood loss of ≥ 500 ml. Results The number of feticides as a percentage of the total number of births during the investigation period was 1.6%. None of the terminations were performed primarily because of a serious risk to the mother's physical health; all of the indications to terminate the pregnancy were based on the psychosocial burden and the risk to the mother's mental health as outlined in Sec. 218a StGB (German Penal Code). The most common fetal diagnoses in the context of a maternal psychosocial emergency were central nervous system abnormalities (29.3%), numerical chromosomal aberrations (29.3%) and structural chromosomal aberrations/syndromes (21.3%). Sonographic measurements were used to estimate fetal weight and the weight of around half of the fetuses was underestimated (- 121.8 ± 155.8 g). The margin of estimation error increased with increasing gestational age (p < 0.001). Misoprostol was the most common drug administered to induce labor. No significant association was found between the method chosen for induction, parity, fetal birth position, fetal anomaly, fetal gender, birth mode or the number of previous cesarean sections and Δdelivery . However, a significantly higher loss of blood was observed with longer Δdelivery (p = 0.02). The likelihood of requiring curettage increased with increasing loss of blood. The number of maternal complications as a percentage of the total patient population was 10.4%. Only 11% of patients agreed to a postmortem examination. Conclusion Late terminations of pregnancy carried out in accordance with Sec. 218a para. 2 StGB are a reality and must be understood and accepted as a possible consequence of modern prenatal medicine. The complication rate after feticide and the subsequent obstetric procedure was 10% for the above-defined maternal complication. Late terminations and their obstetric management should be carried out in specialized perinatal centers which offer interprofessional expertise.

Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome.

BACKGROUND: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy. RESULTS: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by ~40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (~25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Telomere elongation was inducible by telomerase and/or alternative telomere lengthening but was associated with abnormal expression of telomeric genes involved in aging and/or cell growth. Lymphoblastoid cells from NBS patients with long survival times (>12 years) displayed the shortest telomeres and low caspase 7 activity. CONCLUSIONS: NBS is a secondary telomeropathy. The two-edged sword of telomere attrition enhances the cancer-prone situation in NBS but can also lead to a relatively stable cellular phenotype in tumor survivors. Results suggest a modular model for progeroid syndromes with abnormal expression of telomeric genes as a molecular basis. METHODS: We studied TL and function in 38 homozygous individuals, 27 heterozygotes, one homozygous fetus, six NBS lymphoblastoid cell lines, and humanized NBS mice, all with the same founder NBN mutation: c.657_661del5.

Secretory products from human adipocytes stimulate proinflammatory cytokine secretion from human endothelial cells.

Hyperplasia and hypertrophy of fat cells can be found in obesity and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial protein secretion. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, significantly increased secretion of 23 cytokines and chemokines from HUVECs was detected in four independent experiments after Adipo stimulation by protein array analysis detecting a total of 174 different proteins. Among those, time-dependent Adipo-induced upregulation of cytokine secretion in HUVECs was confirmed by ELISA for interleukin (IL)-8, monokine induced by gamma interferon, macrophage inflammatory protein (MIP)-1beta, MIP-3alpha, monocyte chemoattractant protein-1, and IL-6. Factors besides adiponectin, leptin, resistin, and tumor necrosis factor alpha appear to mediate these stimulatory effects. Our findings suggest that endothelial cell secretion is significantly influenced towards a proinflammatory pattern by adipocyte-secreted factors.

Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia.

OBJECTIVE: Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular risk for both mother and newborn. Recently, low levels of endogenous soluble receptor for advanced glycation endproducts (esRAGE) have been associated with increased cardiovascular risk. In the current study, we investigated esRAGE serum levels in patients with preeclampsia as compared to healthy gestational age-matched controls. METHODS: esRAGE was quantified by enzyme-linked immunosorbent assay in controls and patients with preeclampsia during pregnancy (control: n = 20, preeclampsia: n = 16) and 6 months after delivery (control: n = 19, preeclampsia: n = 15). Furthermore, esRAGE was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. RESULTS: During pregnancy, median maternal serum esRAGE concentrations were more than three-fold higher in patients with preeclampsia (200 ng/l) than in controls (63 ng/l) (P < 0.01). Furthermore, esRAGE levels positively correlated with age, blood pressure, creatinine, adiponectin, and C-reactive protein, whereas a negative correlation existed with fasting insulin and the homeostasis model assessment of insulin resistance index. In multivariate analyses, homeostasis model assessment of insulin resistance and C-reactive protein independently predicted esRAGE serum levels and explained 44% of the variation in esRAGE concentrations. Surprisingly, median esRAGE concentrations 6 months after delivery were significantly lower in former patients with preeclampsia (270 ng/l) than in controls (342 ng/l) in contrast to the results obtained during pregnancy. CONCLUSION: We showed that maternal esRAGE concentrations are significantly increased in patients with preeclampsia during pregnancy. Here, insulin sensitivity and inflammatory status independently predict serum esRAGE levels.

Serum levels of the adipokine visfatin are increased in pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is a serious cardiovascular complication in pregnancy which shares risk factors with the metabolic syndrome including insulin resistance and obesity. Recently, visfatin was introduced as a novel insulin-mimetic adipokine which is up-regulated when weight is gained. In the current study, we investigated visfatin serum levels in pre-eclamptic patients as compared to healthy gestational age-matched controls. PATIENTS AND MEASUREMENTS: Visfatin was quantified by ELISA in control (n = 20) and PE (n = 15) patients. Furthermore, visfatin was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. RESULTS: Mean maternal visfatin serum levels adjusted for maternal age were about twofold up-regulated in PE (31.1 +/- 23.4 microg/l) as compared to controls (15.7 +/- 23.1 microg/l). Furthermore, visfatin concentrations correlated positively with age, blood pressure, creatinine, free fatty acids (FFA), IL-6 and C reactive protein (CRP), whereas a negative correlation was found with fasting insulin and the HOMA-insulin resistance index (HOMA-IR). In multivariate analyses, HOMA-IR and CRP remained independently associated with visfatin serum levels and explained 58% of the variation in visfatin concentrations. CONCLUSIONS: We show that maternal visfatin levels are significantly increased in PE patients. Furthermore, insulin sensitivity and inflammatory status independently predict serum visfatin levels.

Serum levels of the adipokine adipocyte fatty acid-binding protein are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication of pregnancy which is associated with an increased future metabolic and cardiovascular risk for both mother and newborn. Recently, adipocyte fatty acid-binding protein (AFABP) was introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In this study, we investigated serum concentrations of the adipokine AFABP in patients with PE as compared to healthy controls of similar gestational age. METHODS: AFABP serum levels were quantified by enzyme-linked immunosorbent assay (ELISA) in control (n = 20) and PE (n = 16) patients. Furthermore, AFABP was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Mean maternal AFABP concentrations were significantly elevated in PE (24.5 +/- 9.7 microg/l) as compared to controls (14.8 +/- 7.1 microg/l). Furthermore, AFABP serum levels correlated positively with age, body mass index (BMI), blood pressure, serum creatinine, free fatty acids (FFAs), leptin, and C-reactive protein (CRP). In multivariate analyses, BMI and serum creatinine remained independently associated with AFABP concentrations and explained 58% of the variation in AFABP levels. CONCLUSION: We demonstrate that maternal AFABP serum concentrations are significantly increased in PE. Furthermore, BMI and serum creatinine are independent predictors of circulating AFABP.

Circulatory soluble endoglin and its predictive value for preeclampsia in second-trimester pregnancies with abnormal uterine perfusion.

OBJECTIVE: Soluble endoglin (sEng) is increased dramatically in preeclampsia and acts synergistically with soluble fms-like tyrosine kinase 1 (sFlt1) to promote the preeclamptic phenotype. The aim of this study was to investigate whether the sEng increase was present already in second-trimester pregnancies with abnormal uterine perfusion and whether the pregnancy was at risk for preeclampsia. STUDY DESIGN: This prospective study includes 77 second-trimester pregnant women with abnormal uterine perfusion. sEng and sFlt1 were measured with an enzyme-linked immunosorbent assay. RESULTS: Adverse pregnancy outcome was associated with higher sEng levels in the second trimester. SEng was highest in those pregnancies with early-onset preeclampsia. Combined analysis of sEng and sFlt1 is able to predict early-onset preeclampsia with a sensitivity of 100% and a specificity of 93.3%. CONCLUSION: Elevated sEng levels are detectable in second-trimester pregnancies with abnormal uterine perfusion and subsequent pregnancy complications. The concurrent measurement of uterine perfusion and angiogenic factors allows a highly efficient prediction of early-onset preeclampsia.

Maternal plasma concentrations of soluble endoglin in pregnancies with intrauterine growth restriction.

CONTEXT: Soluble endoglin (sEng), a coreceptor for TGF with antiangiogenic properties, acts synergistically with soluble fms-like tyrosine kinase 1 (sFlt1) to induce symptoms of HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in animal models and to promote a preeclamptic phenotype. Pregnant women with preeclampsia show increased sEng concentrations in circulation, whereas the sEng increase is detectable months before the clinical onset of the disease. OBJECTIVE: The aim of the study was to determine whether maternal sEng is altered in pregnancies with normotensive intrauterine growth restriction (IUGR). DESIGN: sEng and sFlt1 were retrospectively determined by a commercial ELISA. PATIENTS: The study included 11 normotensive pregnancies with IUGR, 18 pregnancies with manifest preeclampsia, and 15 gestational-age-matched controls. RESULTS: Patients with preeclampsia showed significantly higher sEng concentrations compared with controls (57.0 ng/ml vs. 5.3 ng/ml; P < 0.001). Also IUGR pregnancies showed significantly elevated sEng concentrations (25.9 ng/ml; P < 0.001), but the levels were lower compared with the preeclamptic patients. There was a strong positive correlation between the sEng and sFlt1 concentration (Pearson 0.552; P < 0.01). Similar to sEng, the maternal sFlt1 concentration is highest in the preeclamptic patients (8388 vs. 2602 pg/ml; P < 0.01) but also significantly elevated in the IUGR patients (6952 pg/ml; P < 0.01). CONCLUSIONS: Pregnancy with IUGR, but without maternal symptoms, was characterized by elevated sEng concentrations in circulation. Although this finding is less pronounced when compared with preeclampsia, sEng seems to be involved in different clinical manifestations of placental pathology.

Is parvovirus B19 the cause for autoimmunity against the angiotensin II type receptor?

Initial studies have demonstrated the significance of the agonistic angiotensin II receptor AT1 autoantibody (AT1-AA) in preeclampsia, although it is unclear what factors induce its generation. Since the epitope recognized by AT1-AA shares high homology with parvovirus B19 (PVB19) capsid proteins, we have investigated the relationship between the presence of AT1-AA in maternal circulation and PVB19 sero-prevalence in normal and abnormal pregnancy. We determined the parvovirus IgG sero-prevalence in normal pregnancies in the second trimester and those with abnormal uterine perfusion that are at risk for preeclampsia. Secondly, pregnancies at delivery with preeclampsia or intrauterine growth restriction were included. All women with normal perfusion were AT1-AA-negative and 80% were parvovirus-IgG-positive. Sixty-three percent of pregnancies with abnormal uterine perfusion were AT1-AA-positive and 71% IgG-positive. Fifty-two percent of the IgG-positive pregnancies in this subgroup were also AT1-AA-positive, and 9 of the 10 parvovirus IgG-negative women were AT1-AA-positive. In the third trimester, 87% of pregnancies with manifest disease were AT1-AA-positive and 58% IgG-positive. While 79% of the PVB19 IgG-positive pregnancies were also AT1-AA-positive, all parvovirus IgG-negative women were AT1-AA-positive. In all groups, AT1-AA activity did not differ between parvovirus IgG-negative and positive women. We find parvovirus IgG-positive pregnant women in all subgroups without relation to AT1-AA presence. This favors AT1-AA generation to be independent of epitope mimicry between parvovirus B19 capsid proteins and the AT1 receptor.

A combined technique for predicting pre-eclampsia: concurrent measurement of uterine perfusion and analysis of heart rate and blood pressure variability.

OBJECTIVE: Pre-eclampsia is a serious complication of pregnancy with high morbidity and mortality and an incidence of 3-5% in all pregnancies. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients have pathological uterine perfusion in the second trimester, perfusion disturbance has a positive predictive accuracy (PPA) only of approximately 30%. METHODS: Non-invasive continuous blood pressure recordings were taken simultaneously via a finger cuff for 30 min. Time series of systolic as well as diastolic beat-to-beat pressure values were extracted to analyse heart rate and blood pressure variability and baroreflex sensitivity in 102 second-trimester pregnancies, to assess predictability for pre-eclampsia (n = 16). All women underwent Doppler investigations of the uterine arteries. RESULTS: We identified a combination of three variability and baroreflex parameters to best predict pre-eclampsia several weeks before clinical manifestation. The discriminant function of these three parameters classified patients with later pre-eclampsia with a sensitivity of 87.5%, a specificity of 83.7%, and a PPA of 50.0%. Combined with Doppler investigations of uterine arteries, PPA increased to 71.4%. CONCLUSIONS: This technique of incorporating one-stop clinical assessment of uterine perfusion and variability parameters in the second trimester produces the most effective prediction of pre-eclampsia to date.

Autonomic cardiovascular control in pregnancies with abnormal uterine perfusion.

BACKGROUND: Abnormal uterine perfusion is associated with the development of hypertensive pregnancy disorders. However, its impact on maternal autonomic cardiovascular control is poorly understood. The aim of our study was to investigate the adaptation of autonomic control during pregnancy with abnormal uterine perfusion with normal and pathologic outcome in comparison to normal pregnancies. based on blood pressure variability (BPV), baroreflex sensitivity (BRS), and heart rate variability (HRV) analyses. METHODS: A total of 32 healthy pregnant women (CON, age 28 years, range 24 to 31 years); 16 women with abnormal uterine perfusion and normal outcome (AP-NO, age 29 years, range 28 to 33 years); and 19 women with abnormal uterine perfusion and pathologic outcome (AP-PO, age 26 years, range 25 to 30 years), were recruited for this longitudinal study. Beginning in the 20th week of pregnancy, the women were monitored every fourth week until delivery. For the analysis of BPV, BRS, and HRV, high-resolution ECG, and noninvasive continuous blood pressure (BP) recordings were taken simultaneously for 30 minutes. RESULTS: CON showed pregnancy-induced adaptation of cardiovascular control; in the course of gestation BPV was increased while parameters of HRV and BRS were reduced. On the contrary, no changes during the second half of pregnancy could be observed in pregnancies with abnormal perfusion. Variability parameters were significantly altered in women with abnormal perfusion compared with CON, whereas these changes were more pronounced in AP-PO compared with AP-NO. CONCLUSIONS: Abnormal uterine perfusion, independently of the pregnancy outcome, has a significant impact on maternal cardiovascular control. Measures of BPV, BRS and HRV might be used for improved risk stratification.

Chorioamnionitis-induced changes of fetal extramedullar hematopoiesis in the second trimester of gestation. Is diagnosis from fetal autopsy possible?

Chorioamnionitis, as the most frequent cause of second trimester abortions, is commonly diagnosed by histomorphological examination of placental tissue. We determined whether chorioamnionitis induces a fetal extramedullary hematopoietic response and estimated whether chorioamnionitis can be diagnosed from fetal liver alone. Clinical data and morphological and histological findings of 39 second trimester abortions, caused by chorioamnionitis, were compared with 32 age-matched control cases. Using hematoxylin and eosin staining, naphtol-ASD-chloracetate esterase and "Berliner Blau" reaction, total hematopoiesis, erythropoiesis, myelopoiesis and intracytoplasmatic iron of fetal liver were examined. In the study group, total hematopoiesis was increased compared with the controls (94.9% versus 84.4%). The same was seen in erythropoiesis (69.2% versus 56.2%, P>0.05). Chorioamnionitis resulted in a significant increase of fetal myelopoiesis with clustering of leukocytes in 56.4% (P=0.001). Neutrophiles were located predominantly intrasinusoidal and periportal (74.4%), while an isolated periportal location was often observed in controls (50.0%). Isolated perivenous iron storing was more often seen with chorioamnionitis (28.3% versus 3.1%) and correlated with the increasing severity of chorioamnionitis. It can be stated that infectious diseases, such as chorioamnionitis, increase fetal intrahepatic myelopoiesis as one defense mechanism. The morphology of fetal intrahepatic hematopoiesis and iron storing might also be helpful in the diagnosis of chorioamnionitis, especially when the placenta is not available for examination.

Longitudinal analysis of heart rate variability in chronic hypertensive pregnancy.

In the US, it is currently estimated that 3% of pregnant women have chronic hypertension, or more than 100,000 pregnant women each year. The aim of our study was to investigate the adaptation of autonomic control during pregnancy based on heart rate variability analysis and to determine whether chronic hypertension during pregnancy has an impact on this adaptation. Sixteen pregnant women with chronic hypertension (CH group; mean age, 30 years; range, 25-33 years) and 35 healthy pregnant women serving as controls (CON group; mean age, 28 years; range, 24-30 years) were recruited for this longitudinal study. Beginning at the 20th week of pregnancy, the women were monitored every 4th week until delivery. For the analysis of heart rate variability, Portapres signals (200 Hz) were recorded for 30 min under resting conditions. Women in the CH group had significantly elevated blood pressure compared to controls (CON, 111 mmHg [105-132]; CH, 140 mmHg [132-148]; p<0.001). An increased heart rate was found in both groups during the second half of pregnancy. Consequently, decreased heart rate variability was observed, but was more pronounced in the CON group. There was a shift in the frequency bands indicated by an elevation of the low-to-high frequency ratio (LF/HF) in both groups due to a decrease in HF, and thus a significant increase in LFn (LF power in normalized units). However, VLF (power of very low frequency range) increased exclusively in the CON pregnancies. Our data showed no significant difference in heart rate variability between the subjects of the CH and CON groups. Longitudinal variations were detectable in normal pregnancies and also, albeit to a lesser degree, in chronic hypertensive pregnant women. Thus, our data indicate that patients with long-term hypertension are still able to respond to the physiological changes occurring during pregnancy.