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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.Die sonografische Basisuntersuchung in der Gynäkologie umfasst Diagnostik und Differenzialdiagnostik in der täglichen Praxis: Gesundheitsvorsorge, Abgrenzung der Normalbefunde von pathologischen Befunden wie kongenitale Fehlbildungen, benigne und maligne Tumoren, Adnextorsionen, entzündliche Erkrankungen des inneren Genitals, Endometriose, gestörte Frühgraviditäten und Tubargraviditäten sowie Fragestellungen zu Kontrazeption und Fertilität. Die Standardisierung der Untersuchungstechnik sowie die genaue Definition der Leistungsinhalte für die Basisdiagnostik und für die weiterführende Diagnostik (DEGUM-Stufe II) analog des schon seit Jahren in der pränatalen Diagnostik bewährten Mehrstufenkonzepts der DEGUM sind inzwischen auch in die gynäkologische Sonografie implementiert worden. Als Grundlage für eine strukturierte Aus- und Weiterbildung im Rahmen dieses Stufenkonzepts haben DEGUM, ÖGUM und SGUM die Qualitätsanforderungen und die Leistungsinhalte für gynäkologische sonografische Basisuntersuchungen (DEGUM-Stufe I) entsprechend dem gegenwärtigen Kenntnisstand sowie anhand nationaler und internationaler Standards und Empfehlungen aktualisiert.

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 motherʼs physical health; all of the indications to terminate the pregnancy were based on the psychosocial burden and the risk to the motherʼs 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 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.

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.

Objective: We studied the short-term response of autonomic control to delivery in normal pregnancies and pregnancies with preeclampsia (PE). Methods: Fourteen healthy pregnant women and 13 women with PE were monitored within four days before and four days after delivery and compared to values of 14 non-pregnant women as controls using high-resolution electrocardiogram and noninvasive continuous blood pressure monitoring. Results: In PE, blood pressure remained elevated four days postpartum, but markers for arterial stiffness normalized. In contrast, none of heart rate variability and baroreflex sensitivity parameters, altered due to either pregnancy or disease, were normalized 96 h after delivery. Conclusion: Four days after delivery, the maternal cardiovascular system is still strongly affected by pregnancy independent of the health status.

Objective A single course of antenatal corticosteroids (ACS) is associated with a reduction in respiratory distress syndrome and neonatal death. Multiple Courses of Antenatal Corticosteroids Study (MACS), a study involving 1858 women, was a multicentre randomized placebo-controlled trial of multiple courses of ACS, given every 14 days until 33+6 weeks or birth, whichever came first. The primary outcome of the study, a composite of neonatal mortality and morbidity, was similar for the multiple ACS and placebo groups (12.9% vs. 12.5%), but infants exposed to multiple courses of ACS weighed less, were shorter, and had smaller head circumferences. Thus for women who remain at increased risk of preterm birth, multiple courses of ACS (every 14 days) are not recommended. Chronic use of corticosteroids is associated with numerous side effects including weight gain and depression The aim of this postpartum assessment was to ascertain if multiple courses of ACS were associated with maternal side effects. Methods Three months postpartum, women who participated in MACS were asked to complete a structured questionnaire that asked about maternal side effects of corticosteroid use during MACS and included the Edinburgh Postnatal Depression Scale Women were also asked to evaluate their study participation Results Of the 1858 women randomized, 1712 (92.1%) completed the postpartum questionnaire. There were no significant differences in the risk of maternal side effects between the two groups. Large numbers of women met the criteria for postpartum depression (14.1% in the ACS vs. 16.0% in the placebo group). Most women (94.1%) responded that they would participate in the trial again. Conclusion In pregnancy, corticosteroids are given to women for fetal lung maturation and for the treatment of various maternal diseases. In this international multicentre randomized controlled trial, multiple courses of ACS (every 14 days) were not associated with maternal side effects, and the majority of women responded that they would participate in such a study again.

Eine schwangere Patientin, bei der eine Phenylketonurie bekannt war, wurde in der 16. Schwangerschaftswoche (SSW) wegen Verdacht auf kardiale Fehlbildung des Fetus zur Pranatalsprechstunde uberwiesen. Sonographisch zeigte sich ein Ventrikelseptumdefekt, die Entwicklung entsprach der 14. SSW. In der 25. SSW wurde bei erneuter fetaler Echokardiographie ein „double outlet right ventricle“ (DORV) diagnostiziert, die fetale Biometrie entsprach der 22. SSW. In der 40. +5 SSW kam es zur unauffalligen Spontangeburt eines hypotrophen Jungen mit Gesichtsdysmorphie. Die postnatale Echokardiographie ergab einen Rechtsaortenbogen, einen Ventrikelseptumdefekt und einen Links-rechts-Shunt sowie eine uberreitende Aorta. Der Phanotyp entsprach dem Vollbild einer Phenylketonurie-Fetopathie. Diese Fetopathie ware durch Einhalten einer phenylalaninarmen Diat seitens der Mutter vermeidbar gewesen.

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.

We report on partial duplication 21q resulting from a paternal insertion identified during prenatal diagnosis. While performing interphase fluorescence in situ hybridization (I-FISH), we were able to identify 3 signals of the LSI 21 Spectrum Orange probe with chorionic villus sampling. Using standard cytogenetic analysis, I-FISH and GTG banding, structural aberrations in 21q in the parents and in the fetus could not be reliably determined. Applying metaphase fluorescence in situ hybridization (M-FISH), we identified a recombinant chromosome 21 carrying an interstitial duplication of the Down syndrome critical region inherited from the father. Both data from our analysis and published literature recommend the use of rapid testing methods such as I-FISH and standard cytogenetic analysis in prenatal diagnosis. It became obvious that I-FISH would not detect such a particular aberration. Thus, karyotyping, I-FISH and M-FISH should be performed in all Down syndrome cases.

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.

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.The aim of the study was to determine whether maternal sEng is altered in pregnancies with normotensive intrauterine growth restriction (IUGR).sEng and sFlt1 were retrospectively determined by a commercial ELISA.The study included 11 normotensive pregnancies with IUGR, 18 pregnancies with manifest preeclampsia, and 15 gestational-age-matched controls.Patients with preeclampsia showed significantly higher sEng concentrations compared with controls (57.0 ng/ml vs. 5.3 ng/ml; P0.001). Also IUGR pregnancies showed significantly elevated sEng concentrations (25.9 ng/ml; P0.001), 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; P0.01). Similar to sEng, the maternal sFlt1 concentration is highest in the preeclamptic patients (8388 vs. 2602 pg/ml; P0.01) but also significantly elevated in the IUGR patients (6952 pg/ml; P0.01).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.

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.

Little attention has been paid to the pathologic features of the umbilical cord, which might fatally damage the fetus. We determined the association of hypercoiling (more than 1 coil per 5 cm) and thinning with consecutive constriction of the umbilical vessels (thin cord syndrome; TCS) and intrauterine fetal death (IUFD). Three hundred and three cases of consecutive fetal autopsies over a 5-year period, including spontaneous and induced abortions of the 2nd trimester of pregnancy, were examined using a standardized protocol. The mean maternal age was 28.5 years and the mean gestational age was 19.1 weeks (range: 12.6 to 24.5 weeks). Thirty-six percent of all cases were induced abortions because of congenital malformations, and 8.9% resulted from legal abortions, as regulated by German law. One hundred sixty-seven cases (55.1%) were spontaneous abortion specimens. The leading cause for IUFD in the spontaneous abortion group was an amnion infection (34.7%), followed by abruptio placentae (15.6%). In 25.1% of cases, placental dysmaturity with consecutive placental insufficiency was responsible for IUFD. Pathologies of the umbilical cord as the cause of IUFD were seen in 10.2% of the cases. Most of these cases (15/17) involved TCS. In 14.4% of all spontaneous abortion specimens the cause of IUFD could not be determined by autopsy. There was an apparent difference in the frequency of TCS in the spontaneous abortion group (15/167 = 9%) compared to the nonspontaneous group (2/136 = 1.5%). A remarkably high percentage (17/303 = 5.6%) of all cases showed TCS. In cases of spontaneous abortions, TCS was causative for intrauterine death in 9% of cases (15/167). Careful pathologic examination of the umbilical cord is recommended to detect TCS and to reduce the cases with unexplained intrauterine death.

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.

As there is growing evidence that hypertensive pregnancy disorders are associated with a risk of cardiovascular diseases later, the resolution of hypertension postpartum (PP) is of high clinical significance. However, there is little knowledge about the factors that influence this normalization. The objectives of our study were (a) to investigate whether or not there are differences in the resolution of hypertension between the distinct types of hypertensive pregnancy disorders and (b) to analyse what clinical parameters may determine the resolution pattern PP. In this retrospective study, 52 patients with preeclampsia (PE), seven with HELLP syndrome (haemolysis, elevated liver enzymes, low platelets), 10 with chronic hypertension (CH) and 21 with pregnancy-induced hypertension (PIH) were recruited. The course of the clinical parameters until day 7 PP was documented. Patients with proteinuria (PE/HELLP) showed the highest blood pressure values PP, while patients with PIH and CH showed no blood pressure changes up to day 7 PP. In patients with proteinuric diseases, there was a significantly higher percentage of cases with persisting hypertension at day 3 PP (71% vs 48% PIH/CH group, P

Abnormal uterine perfusion detected by Doppler sonography reflects impaired trophoblast invasion, a factor involved in the pathogenesis of pregnancy complications such as preeclampsia or intrauterine growth retardation. Recent studies have demonstrated an autoantibody against the angiotensin type 1 (AT 1 ) receptor in pregnant women with preeclampsia. Our aim was to determine whether the AT 1 autoantibody precedes the clinical symptoms and is thus predictive of preeclampsia. We therefore detected this antibody in serum from second trimester pregnancies with abnormal uterine perfusion because these women show an indirect sign of inadequate trophoblast invasion. Then the AT 1 autoantibody distribution/concentration was compared with that of women at term with or without pregnancy pathology. The AT 1 autoantibody was already detectable in second trimester pregnant women with abnormal uterine perfusion before the clinical manifestation of preeclampsia (80%). However, it was also found in second trimester pregnant women with abnormal uterine perfusion who later developed intrauterine growth retardation (60%) or even had a normal course of pregnancy (62%). In the third trimester, the AT 1 autoantibody was demonstrated in 89% of patients with manifest preeclampsia, 86% of those with manifest intrauterine growth retardation, and even in healthy pregnant women at term with a history of abnormal uterine perfusion in the second trimester. We conclude that the AT 1 autoantibody is an early but nonspecific marker for preeclampsia. The generation of this antibody seems to be associated with distinct types of pregnancy disorders resulting from impaired placental development. The AT 1 autoantibody may thus be causative for pathological uteroplacental perfusion.

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

Objectives To examine whether pathological perfusion in the second trimester is characterized by an altered plasma antioxidant capacity and to investigate whether the total antioxidant capacity in maternal plasma is related to the clinical outcome of these high-risk pregnancies. Methods This was a prospective cohort study that included 25 pregnancies with normal and 25 pregnancies with pathological uterine perfusion. Doppler ultrasound measurement of uterine perfusion was performed between 18 and 23 weeks of gestation. Total antioxidant capacity in maternal plasma was measured using a specific photometric assay. Results Plasma antioxidant capacity of pregnant women with pathological uterine perfusion (227.3 ± 4.0 µmol/L) was significantly lower compared with the group with normal uterine perfusion (275.2 ± 10.5 µmol/L; P < 0.05). There was a significant negative correlation between antioxidant capacity and mean pulsatility index of the uterine arteries (r = −0.363; P < 0.05). Patients with pathological perfusion and a normal course of pregnancy did not show significantly changed values compared with those patients with later pre-eclampsia or intrauterine growth restriction (235.0 ± 4.9 µmol/L vs. 218.6 ± 6.7 µmol/L). Conclusions Second-trimester pregnancies with pathological uterine perfusion are characterized by a decreased antioxidant capacity in maternal plasma. This reduction is related to the impaired uteroplacental blood flow, but does not reflect the changes characteristic of the oxidative status for diseases like pre-eclampsia since the reduction of the plasma antioxidant capacity is not related to the clinical outcome of these high-risk pregnancies. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

Objective : Evaluation of causes of death in stillborn infants. Methods : During a five-year period, 310 consecutive autopsies of stillborn infants were performed using a standardized protocol with systematic examination of all major cranial, thoracic and abdominal organs including microscopic examination. Results : In 71%, the intrauterine death (ID) occurred up to the end of the 37th week of gestation. Thirty-seven percent (115/310) stillbirths represented with maceration and about one-half with minor or major malformations. Thirty-one percent (53/171) of them were responsible for intrauterine death. In 83% (44/53), the intrauterine death of the malformed fetus occurred before the end of 37th week of gestation, most of them (48/53, 90.6%) were small for gestational age infants. In 75.5% (234/310), the placental villous tree and the umbilical cord represented pathologic conditions. In 191cases (61.1%), utero-placental pathology was responsible for intrauterine death. Intrauterine infections and traumatic lesions were accompanied by intrauterine death in 2.2 and 1.3%, respectively. In 15.2%, unexplained intrauterine death (because of severe maceration, the placenta was not available for autopsy or insufficient clinical data) occurred. Conclusions : Perinatal autopsy may be valuable in three ways: the confirmation of ante-mortem diagnoses; the identification of unexpected disorders; and exclusion of other (perhaps inheritable) conditions which might be have caused the intrauterine death. Clinically valuable information, obtained from the autopsy, can be improved by high autopsy rate and performing perinatal necropsies by specially trained pathologists.

We report on a pair of dizygotic twin boys born after ICSI. One twin was affected with maternal meiosis I-derived free trisomy 21. The other had multiple congenital malformations including a complex heart defect and oesophageal atresia. The advanced maternal age of 37 years predisposed for chromosome 21 meiosis I non-disjunction in twin A. Each of the multiple congenital anomalies in twin B has been described in trisomy 21. However, due to dizygosity demonstrated by a panel of molecular markers mapped on chromosome 21 as well as the results of investigations with 16 short tandem repeat markers localized on various other chromosomes, low level mosaicism or chimerism for this aneuploidy in twin B is unlikely. In addition, the twinning process, which by itself is associated with an increased rate of congenital malformations particularly affecting heart and oesophagus, might be responsible for the multiple congenital anomalies in twin B. Thus, in agreement with the results of several population-based studies from the literature, it appears unlikely that the micromanipulation of ICSI is causally responsible for the different anomalies found in these two boys.

Objective: C-type natriuretic peptide (CNP) is a vasoactive hormone and the endothelial component of the natriuretic peptide system. At present, nothing is known about CNP expression in human reproductive tissue. Since CNP shows antimitogenic and vasodilatative properties, it was the aim of the study to investigate whether CNP expression is altered in placenta and myometrium from pregnancies complicated by intrauterine growth retardation. Methods: CNP expression was examined by RNase protection assay in human placenta and myometrium from six normal term pregnancies, six pregnancies with preterm delivery and six pregnancies complicated by intrauterine growth retardation (IUGR). Results: In placenta and myometrium, CNP expression levels did not differ between term and preterm pregnancies (40 vs. 28 weeks of gestation). In pregnancies with IUGR (34 weeks of gestation) placental CNP expression was significantly decreased (100.00 ± 18.6 vs. 67.09 ± 8.7; p < 0.05). In the myometrium from IUGR pregnancies CNP expression was significantly increased to 191.48 ± 42.5 (vs. 100.00 ± 15.4; p < 0.05). Conclusions: CNP is expressed in human placenta and myometrium with no dependency on gestational age in the third trimester. Pregnancies with IUGR show an opposite regulation of CNP in placenta and myometrium, which indicates an organ-specific function of the peptide in human reproductive tissue.

Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

OBJECTIVE The aim of the study was to analyse the accuracy of prenatal sonography in terminated pregnancies and the influence of factors like personnel and standard of technique and organisation on the quality of prenatal sonography for the detection of fetal anomalies. MATERIAL AND METHODS The retrospective study includes 64 cases with termination of pregnancy from 1989 to 1997. We analyse prenatal sonographic and postnatal pathological findings of fetus, placenta and umbilical cord. Furthermore we compare two time periods (1989-93 and 1994-97) with different ultrasound conditions. RESULTS In 36 cases (56%) the prenatal diagnosis was exact. In 7 cases (11%) autopsy could not confirm all findings (false positive), whereas autopsy detected additional anomalies in 18 cases (28%) (false negative). The diagnosis was not correct in 3 cases (5%), whereby 2 pregnancies were terminated without proved somatic and chromosomal anomalies. Compared to 1989-93 the rate of false-positive (12 vs. 5) as well as false-negative (9 vs. 3) diagnoses decreased significantly (p < 0.002) in cases with major anomalies (heart, central nervous system). CONCLUSION We conclude that the improvement of the level of organisation, personnel and technical equipment has relevant impact on the accuracy of prenatal sonography. Autopsy as a method of quality control is absolutely necessary.

Heart rate variability is a relevant predictor of cardiovascular risk in humans. However, to use heart and blood pressure (BP) variability or baroreflex sensitivity as markers for hypertensive pregnancy disorders, it is first necessary to describe these parameters in normal pregnancy. To accommodate the complexities of autonomic cardiovascular control we added parameter domains of nonlinear dynamics to conventional linear methods of time and frequency domains. The BP of 27 women with normal pregnancy and 14 nonpregnant women were monitored at a high resolution (200 Hz sampling frequency) using a Portapres for 30 min. The pregnant women were divided into groups of 32 or less or greater than 32 weeks of gestation. Pregnant and nonpregnant women were classified into subclasses of maternal age of less than 28 or 28 or more years. Except for two single parameter domains, we found no significant differences in heart rate and BP variability for pregnant women with different gestational age or different maternal age. Moreover, no significant differences in spontaneous baroreflex sensitivity could be found between pregnant women regardless of either their age or gestational age. In contrast, all measures of nonlinear dynamics of heart rate variability as well as all parameter domains of spontaneous baroreflex sensitivity showed significant changes between pregnant and nonpregnant women, whereas BP variability did not differ between those groups. This complex assessment of autonomic cardiovascular regulation has shown that the parameters tested are stable in the second half of normal pregnancy, and might have the potential to be excellent indicators of pathophysiologic conditions.

Inadvertent immunisation of seronegative women with RA27/3 rubella virus live-attenuated vaccine several weeks before and after conception is described. Whereas in 5 cases the vaccine virus was not transmitted vertically, in 1 case vaccination led to the development of persistent fetal infection with prolonged virus shedding for more than 8 months. Sequence analysis carried out on isolates from amniotic fluid, from cord blood leukocytes as well as from infantile urine confirmed an infection by the vaccine strain. At birth, the newborn infant exhibited none of the symptoms compatible with the congenital rubella syndrome and signs indicative for development of late onset disease are not apparent. This observation constitutes the first unequivocal documented case of rubella vaccine virus related to persistent fetal infection.

Uteroplacental insufficiency leads to fetal growth retardation, which is a major cause of perinatal and postnatal morbidity. In the present study we investigated the relationship between prenatal haemodynamic disturbances and postnatal intestinal perfusion and gastrointestinal function in small-for-gestational-age neonates. Prospectively, 114 preterm neonates with a birthweight below 1500 g were assigned to one of two groups according to their prenatal Doppler sonographic measurements: neonates with or without prenatal haemodynamic disturbances. We defined a pathological fetal perfusion by a pulsatility index of uterine arteries, umbilical artery and fetal thoracic aorta above the 90th percentile and by a pulsatility index of middle cerebral artery below the 10th percentile of a normal group. We compared the postnatal respiratory and intestinal adaptation in both groups as well as the blood flow velocity waveforms of the superior mesenteric artery in all neonates. Postnatally, all 36 neonates with prenatal haemodynamic disturbances were classified to be small for gestational age. Thirty-one of these neonates developed abdominal problems with delayed meconium passage, abdominal distension, bilious vomiting and a delay in tolerating in enteral feeding within the first days of life. Six of them needed surgical intervention, but none of these infants revealed typical signs of necrotizing enterocolitis. In contrast, all neonates after normal prenatal perfusion were classified to be appropriate for gestational age. Only 19 of 78 neonates of this group showed signs of intestinal disturbances postnatally. By Doppler sonographic investigations we found significant lower systolic, mean and end-diastolic flow velocities and higher pulsatility indices of the superior mesenteric artery in neonates with prenatal haemodynamic disturbances. This may occur as a result of postnatal persistent redistribution of regional blood flow and results in gastrointestinal problems and may adversely affect gut motility.

The objective of the study was to investigate serum levels of the adipokine retinol-binding protein 4 (RBP4) in patients with preeclampsia (PE) as compared with healthy controls of similar gestational age. Retinol-binding protein 4 serum levels were quantified by enzyme-linked immunosorbent assay in control (n = 20) and PE (n = 16) patients. Mean maternal RBP4 concentrations were not significantly different in PE (24.5 mg/L) as compared with controls (22.3 mg/L). Furthermore, RBP4 did not correlate to clinical and biochemical measures of pregnancy outcome, renal function, glucose, and lipid metabolism, as well as inflammation. Our results do not support a role of RBP4 in the pathogenesis of PE.

We describe a giant bilateral vascular mass in the skin of the chest diagnosed by ultrasound investigation in a fetus of 20 gestational weeks. Ultrasound and colour Doppler investigations detected no signs of early congestive heart failure but rapid and excessive enlargement of the vascular mass. Indications of increased fetal blood volume were found. The fetus had additional minor anomalies. Early in utero manifestation suggests a severe vascular malformation.

Extraluminal calcified meconium is found frequently by prenatal ultrasound in cases with bowel perforation and meconium peritonitis. Intraluminal intestinal meconium calcifications are rarely seen in prenatal sonography. Meconium calcifications result from a mixture of meconium and urine that indicates a connection between intestinal and urinary tract. We report a case of a male newborn prenatally diagnosed with intraluminal echogenic calcifications at 23 weeks of gestation, suggesting an anorectal malformation (ARM) with rectourinary fistula. At birth, the child presented with a complex ARM including high anal atresia with both perineal and rectourethral fistula. Furthermore, a bladder outlet obstruction due to a urethral stenosis was diagnosed. Vesicostomy was performed as an emergency procedure followed by colostomy during neonatal period. Posterior sagittal anorectoplasty was performed at the age of 4 months. Prenatal echogenic calcifications within bowel should raise the suspicion of ARM with rectourinary fistula and bladder outlet obstruction.

This workshop, held in Leipzig (Germany) on 22 September 2003, was organized to link new aspects of causative factors for pre-eclampsia to possible clinical consequences. Since aetiology and pathogenesis of pre-eclampsia are still unclear, basic pre-eclampsia research has been focused on early trophoblast development as well as maternal endothelial dysfunction as relevant factors. However, the increased knowledge of the recent past in terms of the cause of pre-eclampsia and the pathophysiological link to the syndrome has not substantially improved the opportunities for risk assessment, early prediction, and causal therapy of pre-eclampsia. At present, new aspects of trophoblast function, the role of peptide systems, and novel genetic and endocrine studies will hopefully facilitate future options for a better understanding and treatment of this pregnancy complication. The aim of this workshop was to provide an overview on some of these novel and interesting aspects of pre-eclampsia. H. Stepan demonstrated that pre-eclampsia can nowadays be understood as a ‘three-stage problem’, whereby each trimenon generates one so far unsolved problem. Stage one in the first trimester is the unknown origin of the disease. An impaired trophoblast invasion is thought to be the central factor regarding the aetiology of pre-eclampsia. However, the evidence that the early disturbance of placental development is indeed causative is still lacking. Moreover, the role of factors like hypoxia and apoptosis is not as clear as once thought. For instance, new data show decreased apoptosis in pre-eclamptic placentae and contradict to the established opinion that placental apoptosis is increased in pregnancies with pre-eclampsia and IUGR. In the second trimenon, a pathological uterine perfusion raises the problem of stage two. Easily measurable by Doppler sonography, the impaired uterine perfusion as a sign of high impedance within the uteroplacental bed has a low positive predictive value since only 35 per cent of the afflicted women develop pregnancy complication later on. Furthermore, this method for the identification of women at risk is not able to predict which clinical manifestation as a result of placental insufficiency (pre-eclampsia, IUGR, HELLP syndrome) will develop. Thus, additional markers are needed that can improve the specificity of uteroplacental perfusion and can be used in clinical practice as an adjunct to sonography. The problem at ‘stage three’ describes pre-eclampsia as a syndrome with the global maternal endothelial damage as the central pathophysiological feature. Since the number of altered markers in maternal plasma as well as placenta is enormous and various metabolic, endocrine and neuro-vegetative axes are influenced, it is difficult at this stage of the disease to

Objective Exstrophy of the bladder is a rare malformation due to an anterior midline defect. Most cases of this condition with variable expression occur sporadically, but there are some cases indicative of a strong genetic component apart from environmental factors. This is a report about another rare mother–child pair with bladder exstrophy. Methods We present the clinical data of a familial case of bladder exstrophy with an affected mother and her equally affected male fetus. Results Prenatal diagnosis of bladder exstrophy in the fetus was assessed by ultrasound at the 19th gestational week and was confirmed after termination of pregnancy at the 21st gestational week. Conclusion The present case may be additional evidence for an autosomal dominant inherited variant of this malformation complex with implication for counselling of affected patients. Copyright © 2004 John Wiley & Sons, Ltd.