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Background: Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. Methods: Using surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT), we estimated the total prevalence of spina bifida and anencephaly per 10,000 births between 2000 and 2010. We also estimated additional lifetime direct medical costs among individuals with spina bifida, compared with those without, in Germany for the year 2009. Results: During the study period, there were 7478 documented cases of spina bifida and anencephaly among the 9,161,189 births, with an estimated average combined prevalence of 8.16 per 10,000 births (95% confidence interval, 7.98 - 8.35). For the 241 spina bifida-affected live births in 2009 in Germany, the estimated additional lifetime direct medical costs compared with non-spina bifida affected births were €65.5 million. Assuming a 50% reduction in the prevalence if folic acid has been provided to all women before pregnancy, 293 spina bifida cases could have been prevented in Germany in 2009. The estimated lifetime direct medical cost saving for the live births in 2009 was €32.9 million assuming a 50% reduction, or €26.1 million assuming a 40% risk reduction. Conclusion: Europe has an epidemic of spina bifida and anencephaly compared with countries with mandatory folic acid fortification policy. Primary prevention through mandatory folic acid fortification would considerably reduce the number of affected pregnancies, and associated additional costs.

Background: Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. Methods: Using surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT), we estimated the total prevalence of spina bifida and anencephaly per 10,000 births between 2000 and 2010. We also estimated additional lifetime direct medical costs among individuals with spina bifida, compared with those without, in Germany for the year 2009. Results: During the study period, there were 7478 documented cases of spina bifida and anencephaly among the 9,161,189 births, with an estimated average combined prevalence of 8.16 per 10,000 births (95% confidence interval, 7.98 - 8.35). For the 241 spina bifida-affected live births in 2009 in Germany, the estimated additional lifetime direct medical costs compared with non-spina bifida affected births were €65.5 million. Assuming a 50% reduction in the prevalence if folic acid has been provided to all women before pregnancy, 293 spina bifida cases could have been prevented in Germany in 2009. The estimated lifetime direct medical cost saving for the live births in 2009 was €32.9 million assuming a 50% reduction, or €26.1 million assuming a 40% risk reduction. Conclusion: Europe has an epidemic of spina bifida and anencephaly compared with countries with mandatory folic acid fortification policy. Primary prevention through mandatory folic acid fortification would considerably reduce the number of affected pregnancies, and associated additional costs.

Background: Large quantities of cell-free foetal DNA have been detected in amniotic fluid, and it has been proposed that this material may contribute to the pool of cell-free foetal DNA in maternal plasma. Methods: Twelve maternal blood samples were obtained from pregnant women about to undergo an amniocentesis. Cell-free DNA was extracted from the maternal plasma samples and the matched amniotic fluid samples. The amount of cell-free foetal DNA was quantified by real-time PCR assays for the SRY and RHD genes. Results: Amniotic fluid was found to contain vast quantities of cell-free DNA (median concentration = 3,978 copies/ml amniotic fluid). The concentration of cell-free foetal DNA in maternal plasma was much lower (median concentration = 96.6 copies/ml maternal plasma). No significant correlation could, however, be determined between these two pools of cell-free foetal DNA. Conclusions: Our data confirm that amniotic fluid contains prodigious quantities of cell-free foetal DNA, but as no relationship exists between this material and that in the maternal circulation, it is unlikely that the amnion contributes to the presence of cell-free foetal DNA in maternal plasma

Background: Circulatory neutrophils have been reported to be activated in preeclampsia. It has been suggested that maternal plasma levels of elastase may serve as a possible cell-free marker to quantify such activation. Although plasma elastase levels have been found to be elevated in cases with manifest preeclampsia and eclampsia, this has not yet been examined in cases with early and late onset preeclampsia. We have now examined this aspect. Methods: In this retrospective study, maternal plasma samples were examined from eight cases with early onset preeclampsia (<34weeks of gestation), eight cases with late onset preeclampsia (>34weeks of gestation) and an equal number of gestational age matched normotensive term controls. Plasma concentrations of elastase were measured by ELISA using a commercially available assay. Results: Plasma elastase concentrations were significantly elevated the preeclampsia study group when compared to the normotensive control group (median=139.2ng/ml versus median=72.1ng/ml; P=0.0025). These elevations remained significant when the preeclampsia study group was stratified into case with early onset preeclampsia (median=118.8ng/ml versus median=62.2ng/ml; P=0.03), but jailed failed to attain significance for those cases with late onset preeclampsia (median=181.3ng/ml versus median=86.3ng/ml; P=0.061). Conclusions: Our data indicate that elastase levels are elevated in both early and late onset forms of preeclampsia, and imply that the activation of neutrophils may be more acute in the former than in the latter (238 words)

Background: We analysed cell-free DNA (cfDNA) in the plasma of patients with both malignant and benign breast lesions by real-time quantitative PCR to determine whether the finding may have diagnostic and prognostic implications. Methods: Plasma samples were obtained from 33 patients with breast cancer, 32 patients with benign breast lesions and 50 healthy women as normal controls. Circulatory cfDNA was extracted from the plasma samples and quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Results: The mean concentrations of cfDNA in the plasma samples from patients with breast cancer, patients with benign breast lesions and normal controls were 2,285, 1,368 and 1,489 genome equivalents (GE) per millilitre, respectively. The level of cfDNA in the breast cancer group was significantly higher than those in the benign lesion group and control group (P=0.007 and 0.013, respectively). These findings were associated with malignant tumour size. The levels of the cfDNA were high in patients with lymph node involvement and distant metastasis. Conclusions: Our results suggest that levels of cfDNA in the plasma are elevated in malignant breast cancer and correlated with tumour size. These findings could have diagnostic and prognostic value for malignant breast tumours

Purpose: To examine the potential high throughput capability and efficiency of an automated DNA extraction system in combination with mass spectrometry for the non-invasive determination of the foetal Rhesus D status. Methods: A total of 178 maternal plasma samples from RHD-negative pregnant women were examined, from which DNA was extracted using the automated Roche MagNA Pure™ system. Presence of the foetal RHD gene was detected by PCR for RHD exon 7 and subsequent analysis using the Sequenom MassArray™ mass spectrometric system. Results: We determined that as little as 15pg of RHD-positive genomic DNA could be detected in a background of 585pg of RHD-negative genomic DNA. The analysis of the clinical samples yielded a sensitivity and specificity of 96.1 and 96.1%, respectively. Conclusion: Our study indicated that automated DNA extraction in combination with mass spectrometry permits the determination of foetal Rhesus D genotype with an accuracy comparable to the current approaches using real-time PCR

Purpose: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. Methods: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n=70; group B 1998-2006, n=63). Results: Both study groups showed similar results in survival (median recurrent disease-specific survival—A 18 months vs. B 19 months; P=0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P=0.0057], received more therapy lines (≥3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P=0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A=−10.02; 95%CI −17.99 to −2.05; P=0.014). Conclusions: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfilled

Circulatory cell-free DNA (cf-DNA) is increased in a variety of clinical pathologic conditions; therefore, these markers could be widely used as markers for detecting and monitoring several disorders. To better understand the biology of this molecule, we analysed the relationship between the level of circulatory cf-DNA and physiological parameters such as gender, age and frequency of blood donations. Paired plasma and serum samples were obtained from 87 blood donors and 50 healthy adults who had never donated blood. Cf-DNA was extracted from plasma and serum samples using the MagNA Pure LC Instrument. Quantity determination of circulatory cf-DNA was performed by TaqMan real-time PCR for the ubiquitous GAPDH gene. Our data showed that the concentration of cf-DNA in serum was about eightfold higher than that in plasma. Regarding the level of these circulatory species, no significant differences were observed between the age-matched men and women and gender-matched, different-age cohorts, except in women who were older than 60years of age. Frequent blood donations did not increase the circulatory species. Circulatory cf-DNA in plasma and serum samples is not correlated with human gender and human age except in women who are older than 60years of age. Frequent blood donation did not affect the quantity of circulatory cf-DNA. The explanation for the latter most likely is the short half-life time of free fetal DNA in maternal circulation

Human pregnancy is a metabolic and immune challenge for the mother who has to accommodate in her womb a semi-allogeneic fetus whose energy needs increase tremendously with gestation. Recent compelling research has suggested that proper inflammatory changes and oxidative balance are a requisite for successful pregnancy. The placenta is an integral component of this inflammatory response as it actively produces a variety of cytokines and immunomodulatory hormones. In preeclampsia, a life-threatening disorder of pregnancy that is characterized by widespread damage and dysfunction of the maternal endothelium, placental oxidative stress and aberrant cytokine expression induces an exaggerated maternal systemic inflammatory response to pregnancy

Objective: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer. Patients and methods: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for ≥6 months. Results: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). Conclusions: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cancer

Recent studies have suggested that the innate immune system is involved in the pathogenesis of preeclampsia. Its pathogenesis involves neutrophil activation and increased levels of cell-free DNA in the maternal plasma. Activation of neutrophils has recently been shown to induce DNA containing neutrophil extracellular traps (NETs) which trap and kill bacteria. Massive NETs induction by the placentally derived factors (IL-8 and placental micro-debris) and their increased presence in preeclamptic placenta suggest that NETs might be involved in the pathogenesis of preeclampsia. Therefore, increased presence of NETs in preeclampsia may play a role in the deficient placental perfusion associated with this disorder

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P=0.0003, TV: P=0.0009, TSA: P<0.0001; multivariate analyses: MD: P=0.0018, TV: P=0.0109, TSA: P=0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone

Introduction: Iron-deficiency anaemia during pregnancy and postpartum occurs frequently and may lead to severe maternal and foetal complications. New treatment regimens include intravenous iron administration in particular clinical situations. The aim of the study was to determine optimal diagnostic and therapeutic approaches to iron-deficiency anaemia during pregnancy and postpartum. Methods: The evidence from data available from published studies and recommendations regarding diagnosis and treatment were reviewed. As conclusions, recommendations are given by an expert panel. Results: During pregnancy, oral iron therapy is given as first-line treatment. In cases with lack of efficacy, unwarranted side effects or very low haemoglobin values, intravenous iron treatment with iron carboxymaltose is a preferable alternative, although data regarding safety are limited. In the postpartum period, haemoglobin values less than 95g/L are treated ideally by intravenous carboxymaltose, leading to more rapid haemoglobin recovery. Conclusion: New intravenous iron preparations such as iron carboxymaltose have an excellent efficacy, side effect profile and advantages as compared to oral iron preparations for particular clinical indications

Objective: To assess the impact of three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) on maternal-fetal bonding. Study design: Prospective randomized pilot study among low risk women with singleton fetuses in the second and third trimester. Dependent on the randomization pattern, US was commenced either with 2D US or 3D US and the effects were recorded with standardized questionnaires. Results: Sixty patients were included. Although the quality of 2D US, assessed by the examinator, was superior to 3D US, maternal recognition was higher with 3-D US (P=0.004). With 2D US, nulliparous patients had significantly more difficulties visualizing the fetus, than multiparous (P=0.03). However, the maternal preference of 3D US had no significant impact on maternal-fetal bonding. Conclusion: Ultrasound had no significant effect on maternal-fetal bonding. Three-dimensional images may facilitate recognition of the fetus, but 3D US did not have higher impact on maternal-fetal bonding. This finding may be a reason not to consider 3D ultrasound for routine scanning

Purpose: Prolonged first and second stage of labor, isolated prolongation of the second stage, forceps delivery or vacuum extraction, perineal laceration, nulliparity and epidural anesthesia are known risk factors for developing prolonged postpartum urinary retention (PUR). The aim of our study was to analyze number and constellations of these risk factors, in prolonged postpartum urinary retention (PPUR) in our own unit to facilitate the identification of patients at high risk and thus to prevent bladder overdistension by early intervention. Methods: We performed a retrospective analysis of all our cases with PPUR between 2003 and 2008 including variables like age weight, height, body mass index, fetal birth weight and head circumference. Results: The incidence of PPUR at our institution is low being 0.06%. No woman combined all six risk factors. The majority had five risk factors, all had at least four. An isolated prolonged second stage of labor was common to all patients with PPUR. Five women had an epidural anesthesia, three were nulliparous and only two women delivered spontaneously. All but one woman suffered from perineal tears. Interestingly, fetal head circumference was larger than 36cm in four of six cases. Conclusion: In contrast to simple PUR, the prolonged form of PUR could be the result of a cumulative effect of different single risk factors

Objective: To prospectively assess the effect of water birth on maternal and fetal outcomes in a selected low-risk collective of a tertiary obstetrical unit. Method: In this prospective observational study, 513 patients of a low-risk collective, who requested a water birth, were studied during the years 1998-2002. Primary outcome measurements included the maternal and fetal parameters. Secondary outcome measurements comprised data on the incidence of water births in an interested, low-risk population in an academic hospital. Result: All groups were similar in terms of demographic and obstetric data. Significant differences were observed in maternal outcome parameters, which included the use of analgesia/anesthesia during labor, the duration of first and second stages of labor, perineal tears and episiotomy rate. No differences were seen in all observed fetal outcome parameters including APGAR scores, arterial and venous pH, admission rate to neonatal intensive care unit and infection rate. Conclusion: Water birth is a valuable and promising alternative to traditional delivery methods. The maternal and fetal outcomes were similar to traditional land births. However, currently there still exist some deficits in the scientific evaluation of its safety. Therefore, the selection of a low-risk collective is essential to minimize the risks with the addition of strictly maintained guidelines and continuous intrapartum observation and fetal monitoring. Based on our results and the literature, water births are justifiable when certain criteria are met and risk factors are excluded

Background: Maternal serum concentrations of macrophage migration inhibitory factor (MIF) have recently been reported to be elevated in cases with preeclampsia. These findings may be important in increasing our understanding of the underlying events leading to the development of preeclampsia, as this cytokine is also expressed in the placenta, where it has been shown to possess immunemodulatory activities. For this reason we attempted to independently verify this report. Methods: Plasma levels of MIF were assessed by ELISA in plasma samples collected from normal healthy male and female blood donors (n=20 per group), as well as healthy normal pregnant women in all three trimesters of pregnancy (n=60). In addition, MIF levels were examined from cases with mild and severe preeclampsia (n=20 per study cohort) and matched normotensive pregnancies (n=20). Results: MIF levels were found to be elevated in pregnancy (median=10.1ng/ml) when compared to non-pregnant controls (median=1.7ng/ml). A moderate, but not significant, elevation was found to occur from the first to the third trimester of pregnancy. No significant difference was found to occur between the two preeclampsia study groups when compared to the normotensive control group. Conclusions: Our data suggest that circulatory MIF concentrations are elevated throughout pregnancy, but are not further increased in preeclampsia

Objective: Although elective cesarean section (ECS) is the currently recommended modality for delivering women infected with the human immunodeficiency virus (HIV), historical evidence suggests that they are at higher risk of postoperative complications than noninfected women. Those risks have to be carefully balanced against the presumed minimal benefit of ECS, especially in the case of low viral load and high CD4 counts. We therefore compared the incidence and type of post-ECS complications in HIV-infected women, most with low viral loads and high CD4 cell counts, with those in matched noninfected women treated by the same surgical teams. Study design: A Swiss 8-center, prospective, matched case-control study compared minor and major post-ECS complication prevalence, hospital stay and confounding factors (surgeon experience) between HIV-infected and noninfected women. Results: Minor complications in the 53 matched pairs were eightfold more frequent overall in infected women. More frequent specific minor complications were anemia, blood loss and urinary tract infection. Yet the surgeons performing ECS in infected women were more experienced. Complications prolonged hospital stay in infected women. Major complication rates did not significantly differ between the groups. Conclusion: HIV-positive women have a higher risk of post-ECS morbidity, even with high CD4 counts and low viral load. Therefore, the blanket recommendation of ECS in HIV-infected women requires a review

The examination of fetal cells, specifically erythroblasts, and cell-free fetal DNA from the blood of pregnant women is currently the subject of intense research with the aim of developing new risk-free methods for prenatal diagnosis. An unexpected finding made during these studies was that the traffic of fetal erythroblasts into the maternal peripheral circulation was enhanced in pre-eclampsia. Independent prospective studies examining samples collected in the second trimester indicated that this perturbation in fetal cell trafficking occurs early in pregnancy, well before the onset of pre-eclampsia symptoms. The quantitative analysis of cell-free fetal and maternal DNA levels indicated that these concentrations were elevated in a co-ordinate manner in manifest pre-eclampsia, and that these elevations corresponded to disease severity. On the other hand, analysis of prospectively collected samples indicated that only cell-free fetal but not maternal DNA levels were elevated before onset of symptoms in pregnancies which subsequently developed pre-eclampsia. These data support hypotheses suggesting that pre-eclampsia is a multi-step disorder, initiated by a placental lesion that occurs early in pregnancy and which subsequently leads to a systemic maternal inflammatory response and associated endothelial cell damage

Aims: To assess pregnant women's awareness of and attitudes towards cesarean section (CS) on demand, as well as to identify specific target groups by focusing on differences dependant on the participants' background, parity and intended mode of delivery. Methods: The study was conducted at two centers during three months. German-speaking pregnant women were invited to answer an anonymous, structured questionnaire. We compared urban vs. rural, nulliparous vs. parous and women opting for a CS vs. denying this wish, with regard to awareness and attitudes towards CS on demand. Results: Ninety-two percent of the 201 participants were aware of the possibility to deliver by CS on demand. Their sources of information were mostly print media reports, television, or friends. Pain avoidance and missing the birth experience were the main reasons for and against CS on demand, respectively. For women opting for CS on demand, traumatically-experienced previous birth and the child's well-being were other important reasons for a CS. Conclusions: Because negative birth experience appears to be decisive for pregnant women's attitude towards CS on demand and their perception of CS seems to be partly based on misconceptions, antenatal counseling should focus on these aspects

Background: Single nucleotide polymorphisms (SNPs) of mitochondrial DNA (mtDNA) are involved in physiological and pathological conditions. We developed a rapid, accurate, highly sensitive and high-throughput approach with low cost to identify mtDNA SNPs. Methods: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to detect 18 SNPs of mtDNA by uniplex and multiplex assays. The sensitivity and specificity of the MALDI-TOF MS were evaluated. The accuracy of the approach was validated by the comparison of using the robust sequencing analysis. Results: The detection limit achieved with the assays corresponded to the identification of five-genome equivalence of mtDNA per reaction after first round PCR amplification. The testing system enabled the discrimination of as little as 5% of mtDNA polymorphism in the predominating background of mtDNA not containing the SNP. No false positive and false negative results were obtained using the uniplex and multiplex MALDI-TOF MS assays for the analysis of the 18 SNPs compared with those obtained by sequencing analysis. Conclusions: Possible fields which could benefit from this powerful and sensitive tool include forensic medicine, tracing of matrilineage, transplantation immunology, transfusion medicine, the diagnosis of mtDNA mutation related disorders, and the research regarding aging, apoptosis and carcinogenesis based on physiologic and pathogenic alterations of mtDNA for the analysis of large-scale samples, multiple SNPs or rare mtDNA. Clin Chem Lab Med 2008;46:299-305

Objective: To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum. Method: A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4cm dilation) and ending with delivery. Results: A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use. Conclusion: Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters

Background: Limited DNA resources or limited DNA targets in predominant backgrounds for genetic tests can lead to misdiagnosis. We developed a strategy to selectively increase the amount of minor targets through a specific pre-amplification procedure. Methods: We used the model of circulating cell free (ccf) male fetal DNA as a minor target in the predominant maternal plasma DNA to evaluate the strategy. The sex determining region (SRY) locus on the Y chromosome was used to identify ccf fetal DNA, and the human glyceraldehydes-3-phosphate dehydrogenase (GAPDH) gene was used to identify ccf total DNA in maternal plasma. We selectively pre-amplified the minor target SRY locus using the Expand Long Template PCR system and assessed the efficiency of the pre-amplification by real-time PCR, for both SRY and GAPDH, to compare the quantities of pre-amplified fetal DNA with those of maternal total DNA without pre-amplification. Results: The selected pre-amplification increased the amount of ccf fetal DNA dramatically (Wilcoxon test: p=0.000, the fold change=11,596). After selected pre-amplification, a proportion of 2.19% of the ccf fetal minor part in the predominant maternal component was changed up to 25,334%. The increased amounts of ccf fetal DNA found with the pre-amplification are not correlated to the amounts found without the procedure (r=−0.017, p=0.949). Conclusions: This strategy may be useful in genetic analysis with limited DNA resources and limited DNA targets in predominant background molecules. However, this approach is not suitable for quantitative assessments, due to the fact that quantitative imbalanced amplification was observed as a result of the pre-amplification procedure. Clin Chem Lab Med 2009;47:288-93

Background: Existing guidelines recommend different strategies to prevent early-onset neonatal GBS sepsis. In 1997, using our own data on incidence and risk factors, we established a new prevention strategy which includes GBS screening at 36 weeks' gestation and intrapartum antibiotic prophylaxis (IAP) in women with positive or unknown GBS colonization with at least one risk factor. The present study evaluates the efficacy of the new prevention strategy. Methods: Retrospective study of the incidence of early-onset GBS sepsis among all live births at the University Women's Hospital Basel between 1997 and 2002. Additional analysis of delivery and post partum period of all GBS sepsis cases, including GBS screening, risk factors during labor (prematurity, rupture of membranes (ROM) <12 h, intrapartum signs of infection), and IAP. Comparison of this group's characteristics G2 (9,385 live births, using the new strategy) with the previous group, G1 (1984-1993, 16,126 live births, without GBS screening or routine IAP) was performed. Results: The incidence of early-onset GBS sepsis was reduced from 1/1000 (G1) to 0.53/1000 (G2). We observed a significant reduction of overall intrapartum riskfactors in cases of GBS sepsis. Conclusion: This study suggests that our new prevention strategy is effective in reducing the incidence of early-onset GBS sepsis in neonates. In comparison, implementation of the CDC's prevention strategy might have prevented 2 additional cases in 9385 live births. However, this would have required treating a much larger number of pregnant women with IAP with consequential increasing costs, side effects and complications

Fetal cells, specifically fetal erythroblasts, as well as cell-free fetal DNA are present in the maternal circulation. Both are currently being investigated as a means for the non-invasive risk-free analysis of fetal genetic traits. The origin of this cell-free fetal DNA in the maternal circulation is currently unclear. Since numerous fetal erythroblasts have been demonstrated to exhibit an apoptotic phenotype in the form of fragmented nuclear DNA, it has been proposed that such trafficking fetal cells may be a possible source. This hypothesis is supported by reports of elevated numbers of fetal erythroblast and cell-free fetal DNA concentrations in pregnancies affected by pre-eclampsia or polyhydramnios. To address this question, we have examined fetal erythroblast numbers and cell-free DNA concentrations in the same maternal blood samples. Our study, performed on both normal and pathologically-affected pregnancies, indicates that no correlation exists between these two fetal cellular and molecular species. This is most evident in pregnancies affected by onset of preterm labour, where significant elevations in cell-free fetal DNA concentrations were detected without any concomitant elevation in fetal erythroblast numbers. Our data therefore suggest that an alternative cell type is the source of cell-free fetal DNA. Furthermore, it appears that the release of cell-free fetal DNA from this cell type is affected by pathological placental conditions which are not associated with an increase in fetal cell trafficking

There is a rising interest in a balanced and varied women's diet not only preconceptionally but also during pregnancy and in the breastfeeding period in order to reduce fetal, neonatal, and maternal risks. A decreased intake of omega 3-fatty acids (FA) or deficiencies of micronutrients are a global health problem, not only in developing countries, where micronutrient-rich food and fortified aliments are often not available, and also in the industrialized world. In contrast to data about the daily periconceptionally intake of folate acid that has been shown to reduce substantially the occurrence and recurrence of neural tube defects (NTD), the benefit of other micronutrients is less determinant. Deficiencies of omega 3-FA may be a contributing factor for severe complications in pregnancy and postpartum. A meta-analysis for the role of omega 3-FA in preeclampsia and maternal postpartum depression is less consistent, some meta-view's results differ substantially or are even contradictory to large observational studies. Further well-designed studies are warranted. A personal interview and counseling concerning the daily diet should be integrated in the preconceptional and in the antenatal care and an individual supplementation should be offered, if indicated

Single cell PCR is a powerful method for determining the genetic properties of individual cells. In the instance of heterozygous loci, however, preferential amplification of one allele can lead to allele drop out (ADO) of the other allele. Fortunately ADO does not occur in all amplifications, and is usually random when it does occur, with both alleles being equally susceptible to drop out. Therefore pooling of results from multiple independently amplified cells should greatly improve the analysis of diallelic loci, and the misdiagnosis rate of diallelic loci should decrease exponentially with the number of cells analysed. We have shown that this is true and that multiplex PCR allows for the simultaneous identification of a cell in a mixture of cells using microsatellite loci known to be informative, and accurate genotyping at other loci. This approach has practical applications to non-invasive prenatal diagnosis where small numbers of fetal cells in the presence of maternal cells must be both identified and genotyped at loci involved in genetic disease

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations

Warum bleibt der Kinderwunsch vieler Paare unerfüllt, während sich andere gegen Kinder entscheiden? Das Buch präsentiert die Ergebnisse einer Arbeitsgruppe der Berlin-Brandenburgischen Akademie der Wissenschaften und der Leopoldina zu den Gründen niedriger Geburtenraten in Deutschland, Österreich und der Schweiz. Es führt auf einmalige Weise den heutigen Wissensstand aus Medizin, Soziologie, Demografie, Ökonomie, Psychologie, Politik- und Geschichtswissenschaften zusammen, räumt mit Legenden auf, beleuchtet Probleme der Datenerhebung und entwickelt schließlich Empfehlungen, wie die Realisierung von Kinderwünschen besser ermöglicht werden kann. Der Ländervergleich zeigt eindrücklich, dass eine erfolgreiche Familienpolitik neben den Dimensionen Zeit, Geld und Infrastruktur unbedingt den jeweiligen sozialen Kontext berücksichtigen muss.

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations Udgivelsesdato: 2008, This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations Udgivelsesdato: 2008, This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

Die vorzeitige Reifung der Zervix steht im engen Zusammenhang mit den komplexen Mechanismen der Frühgeburtlichkeit. Die transvaginalsonographische Evaluation der Zervix ermöglicht im Gegensatz zur digitalen Tastuntersuchung eine objektive Dokumentation des Befundes nach Visualisierung der Zervix. Dies gilt insbesondere für die exakte Messung der Zervixlänge und die Beurteilung des Os internum. Veränderungen wie eine Trichterbildung, ein Fruchtblasenprolaps oder eine (a)-symptomatische vorzeitige Zervixreifung können sichtbar gemacht und im Trend beurteilt werden. Die transvaginalsonographische Befunderhebung ist leicht erlernbar, objektiv und gut reproduzierbar. In ersten Teil der vorliegenden Arbeit wurde untersucht, in wieweit bei einem low-Risk Kollektiv vorzeitige Reifungszeichen der Zervix vor anderen Frühgeburtsmarkern zu beobachten sind. Die Zervixbeurteilung mit 22 oder 32 SSW konnte nicht als valider Frühgeburtsmarker für ein Screening im strikten low-Risk Kollektiv festgesetzt werden. Auch die rechtzeitige und sichere Diagnose einer drohenden Frühgeburt bei symptomatischen oder asymptomatischen Schwangeren mit vorzeitiger Zervixreifung ist bislang nicht verlässlich möglich. Im zweiten Teil dieser Arbeit wurde bei einem high-Risk Kollektiv von Patientinnen mit vorzeitigen Wehen und Zervixreifung die Aussagekraft der transvaginalsonographische Zervixbiometrie untersucht. Die Zervixbiometrie begründet sich auf der Tatsache, dass die Reifezeichen der Zervix, wie Verkürzung der Zervixlänge, Öffnung des inneren Muttermundes und Dilatation des Zervikalkanals, bei nahenden Geburtswehen unabhängig von der Schwangerschaftsdauer zunehmen. Nach diesen Ergebnissen kann der Einsatz der TVS zur frühzeitigen Erkennung einer drohenden Frühgeburt empfohlen werden. Ihr Nutzen liegt in der Identifizierung von symptomatischen und asymptomatischen Patientinnen mit hohem Frühgeburtsrisiko. Ihnen sollte eine Maximaltherapie angeboten werden. Auf der anderen Seite können Patientin, The premature cervical ripening has a close connection with the complex mechanism of premature delivery. The transvaginal sonographic evaluation of the cervix enables, unlike the digital examination, an objective documentation of the evidence after visualisation of the cervix. This goes especially for the exact measurement of cervical length and the assessment of the internal os. Changes like funneling, prolapse of the amniotic sac or an (a-)symptomatic premature cervical ripening can be visualised and assessed. The transvaginal sonographic evaluation is easily learned, objective and well reproducible. In the first part of the paper it was examined how far in a low risk group premature ripening signs of the cervix can be observed before other premature delivery markers. The cervix assessment with 22 or 32 weeks of gestation could not be fixed as valid premature delivery marker for a screening in the strict low risk group. Also the timely and sure diagnosis of an imminent premature delivery in symptomatic and asymptomatic pregnant women with premature cervix ripening is not reliably possible until now. In the second part of this paper the meaningfulness of the transvaginal sonographic cervix biometry was examined in a high risk group of patients with premature labour pains and cervix ripening. The cervix biometry is based on the fact that the signs of cervix ripening as shortening of cervix length, opening of the internal os and dilatation of the cervix canal increase when delivery pains are approaching, regardless of the duration of pregnancy. According to these results the use of transvaginal sonography for the early detection of an imminent premature delivery can be recommended. Its benefit lies in the identification of symptomatic and asymptomatic patients with a high risk of premature delivery. A maximum therapy should be offered them. On the other side, patients with a low premature delivery risk can be recognized. They can be treated as an outpatient and contr

Die vorzeitige Reifung der Zervix steht im engen Zusammenhang mit den komplexen Mechanismen der Frühgeburtlichkeit. Die transvaginalsonographische Evaluation der Zervix ermöglicht im Gegensatz zur digitalen Tastuntersuchung eine objektive Dokumentation des Befundes nach Visualisierung der Zervix. Dies gilt insbesondere für die exakte Messung der Zervixlänge und die Beurteilung des Os internum. Veränderungen wie eine Trichterbildung, ein Fruchtblasenprolaps oder eine (a)-symptomatische vorzeitige Zervixreifung können sichtbar gemacht und im Trend beurteilt werden. Die transvaginalsonographische Befunderhebung ist leicht erlernbar, objektiv und gut reproduzierbar. In ersten Teil der vorliegenden Arbeit wurde untersucht, in wieweit bei einem low-Risk Kollektiv vorzeitige Reifungszeichen der Zervix vor anderen Frühgeburtsmarkern zu beobachten sind. Die Zervixbeurteilung mit 22 oder 32 SSW konnte nicht als valider Frühgeburtsmarker für ein Screening im strikten low-Risk Kollektiv festgesetzt werden. Auch die rechtzeitige und sichere Diagnose einer drohenden Frühgeburt bei symptomatischen oder asymptomatischen Schwangeren mit vorzeitiger Zervixreifung ist bislang nicht verlässlich möglich. Im zweiten Teil dieser Arbeit wurde bei einem high-Risk Kollektiv von Patientinnen mit vorzeitigen Wehen und Zervixreifung die Aussagekraft der transvaginalsonographische Zervixbiometrie untersucht. Die Zervixbiometrie begründet sich auf der Tatsache, dass die Reifezeichen der Zervix, wie Verkürzung der Zervixlänge, Öffnung des inneren Muttermundes und Dilatation des Zervikalkanals, bei nahenden Geburtswehen unabhängig von der Schwangerschaftsdauer zunehmen. Nach diesen Ergebnissen kann der Einsatz der TVS zur frühzeitigen Erkennung einer drohenden Frühgeburt empfohlen werden. Ihr Nutzen liegt in der Identifizierung von symptomatischen und asymptomatischen Patientinnen mit hohem Frühgeburtsrisiko. Ihnen sollte eine Maximaltherapie angeboten werden. Auf der anderen Seite können Patientin, The premature cervical ripening has a close connection with the complex mechanism of premature delivery. The transvaginal sonographic evaluation of the cervix enables, unlike the digital examination, an objective documentation of the evidence after visualisation of the cervix. This goes especially for the exact measurement of cervical length and the assessment of the internal os. Changes like funneling, prolapse of the amniotic sac or an (a-)symptomatic premature cervical ripening can be visualised and assessed. The transvaginal sonographic evaluation is easily learned, objective and well reproducible. In the first part of the paper it was examined how far in a low risk group premature ripening signs of the cervix can be observed before other premature delivery markers. The cervix assessment with 22 or 32 weeks of gestation could not be fixed as valid premature delivery marker for a screening in the strict low risk group. Also the timely and sure diagnosis of an imminent premature delivery in symptomatic and asymptomatic pregnant women with premature cervix ripening is not reliably possible until now. In the second part of this paper the meaningfulness of the transvaginal sonographic cervix biometry was examined in a high risk group of patients with premature labour pains and cervix ripening. The cervix biometry is based on the fact that the signs of cervix ripening as shortening of cervix length, opening of the internal os and dilatation of the cervix canal increase when delivery pains are approaching, regardless of the duration of pregnancy. According to these results the use of transvaginal sonography for the early detection of an imminent premature delivery can be recommended. Its benefit lies in the identification of symptomatic and asymptomatic patients with a high risk of premature delivery. A maximum therapy should be offered them. On the other side, patients with a low premature delivery risk can be recognized. They can be treated as an outpatient and contr

Introduction: We develop a multiplex quantitative real-time PCR for synchronized analysis of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) to investigate relative mtDNA abundance in paired normal and cancerous breast tissues. Materials and methods: The amounts of nDNA and mtDNA in 102 tissue samples were quantified for both glyceraldehype-3-phosphodehydrogenase (GAPDH) gene and mtDNA encoded ATPase (MTATP) 8 gene. The average threshold cycle (Ct) number values of the nDNA and mtDNA were used to calculate relative mtDNA content in breast tissues. Results: The median delta Ct (ΔCt) and the median mtDNA content for normal and cancerous breast tissues were 6.73 and 2.54, as well as 106.50 and 5.80 (P=0.000, respectively). The mtDNA content was decreased in 82% of cancerous breast tissues compared with the normal ones. The changes were associated with hormone receptor status. Conclusion: Our finding suggests that decreased mtDNA content in breast cancer may have diagnostic and prognostic value for the disease

Background: We have recently explored the detection of circulatory male fetal cells directly in maternal whole blood samples by fluorescence in-situ hybridization (FISH). In order to improve the efficacy of fetal cell detection, we have now examined whether this could be enhanced by the use of two different Y chromosome-specific FISH probes (α-satellite and classical satellite III regions) in combination with an X chromosome-specific FISH probe. Methods: Nineteen maternal blood samples (median gestational age=28weeks, range=12-37weeks) were examined in a blinded manner. No enrichment procedure was performed. Following hypotonic treatment and Carnoy's fixation, total nucleated cells were examined by two color FISH with a single X and two Y chromosome-specific probes. Nine cases were examined in parallel by conventional XY-FISH. Results: Fetal cell detection was superior when using two Y chromosome-specific probes (specificity=75%; sensitivity=91%) when compared to the conventional XY-FISH approach (specificity=50%; sensitivity=60%). Conclusions: Male fetal cells can be detected in most maternal blood samples examined. Specificity and sensitivity is improved when using a combination of single X and two Y chromosome-specific probes when compared to a conventional XY-FISH protocol

Recent studies have provided new insight into aberrations in the immunological interplay between mother and fetus and their potential role in the development of recurrent fetal loss and preeclampsia. The action of anti-phospholipid antibodies in recurrent fetal loss is now proposed to involve the complement system, neutrophil activation and the production of TNFα by immune bystander cells. A clear involvement of the immune system is emerging in preeclampsia, involving mainly the innate arm, especially neutrophils. The activation of peripheral neutrophils by placentally released inflammatory debris triggers the induction of neutrophil extracellular traps (NETs), which may lead to an occlusion of the intervillous space, thereby further promoting a condition of placental hypoxia. It has, hence, been suggested that new therapeutic strategies be developed, including the possible use of TNFα antagonists in cases of recurrent miscarriage. These strategies need to be addressed with caution due to the possible induction of fetal congenital abnormalities

Although perineal ultrasound has been widely used, no standard values have been published. In 52 women with urinary stress incontinence the following parameters were measured during resting and straining: a) with ultrasound: distance (Dy) between bladder neck and central line of the symphysis, distance (Dx) between bladder neck and lower border of the symphysis, and retrovesical angle β; b) with urethrocystography (UCG): distance H between the bladder neck and the SCIPP line, inclination angle α and retrovesical angle β. Dy and H correlated during resting (r=0.608; p<0.001) and straining (r=0.575; p<0.001). The distance Dy of 11mm corresponded to a bladder neck position on the SQIPP line. A rotational descent was detectable when Dx increased from 13mm (± 6.5) during resting to 16mm (±7.8) during straining (p=0.009). It was concluded that perineal ultrasound is valuable for the anatomical evaluation of the bladder neck. This is the first report to better define the position of the bladder based on ultrasonographic measurements

Background: Preeclampsia is characterized by damage to the maternal endothelium that has been suggested to be mediated in part by elevated shedding of inflammatory placental syncytiotrophoblast micro-particles (STBM) into the maternal circulation. Previously, we have shown that STBM, prepared by three different methods: mechanical dissection, in vitro placental explants culture and perfusion of placenta, can inhibit endothelial cell proliferation. Only mechanically prepared STBM induced apoptosis in the endothelial cells. Now, we have examined lipid levels in the three STBM preparations and their differential responses on endothelial cells. Methods: We examined the lipid levels in the three STBM preparations using thin layer chromatography. Furthermore, the effects of reduced lipid levels in the three STBM preparations using the pharmacological agent methyl-β-cyclodextrin were examined on endothelial cell proliferation and apoptosis. Results: Among the three STBM preparations, mechanical STBM contained highest levels of lipids. The reduction in lipid levels in mechanical STBM reduced their potential to inhibit human umbilical vein endothelial cells (HUVEC) proliferation and blocked their potential to induce apoptosis. No similar effect was observed following lipid reduction in the two other STBM preparations. Conclusions: As it has been suggested that mechanically derived STBM may more closely resemble placental micro-particles generated in preeclampsia, our data suggest that lipid content may play a role in the anti-endothelial defects present in this disease

We have assessed a new technique for the isolation of fetal erythroblasts from maternal blood for the non-invasive prenatal diagnosis of pregnancies at risk of β-thalassaemia. This method relies on the separation of erythroblasts from maternal nucleated cells by a novel step gradient and high speed centrifugation. In four of the six cases examined, single erythroblasts were identified by immunohistochemistry for zeta (ζ) globin. These were individually micromanipulated and analysed by single cell polymerase chain reaction (PCR) and subsequent sequencing of the region of β-globin locus where the mutations most common to the region of Puglia, Italy, are clustered. In each of the four instances where fetal erythroblasts were identified by antibody staining, the fetal β-globin genotype was correctly determined. To date, this represents the largest series of non-invasive prenatal diagnoses performed for this haemoglobinopathy

Objective: To compare the efficacy of vaginal misoprostol versus dinoprostone for induction of labor (IOL) in patients with preeclampsia according to the WHO criteria. Study design: Ninety-eight patients were retrospectively analyzed. A total of 47 patients received 3mg dinoprostone suppositories every 6h (max. 6mg/24h) whereas 51 patients in the misoprostol group received either 50μg misoprostol vaginally every 12h, or 25μg every 6h (max. 100μg/24h). Primary outcomes were vaginal delivery within 24 and 48h, respectively. Results: The probability of delivering within 48h was more than three-fold higher in the misoprostol than in the dinoprostone group: odds ratio (OR)=3.48; 95% confidence interval (CI) 1.24, 10.30, whereas no significant difference was observed within 24h (P=0.34). No correlation was seen between a ripe cervix prior to IOL and delivery within 24/48h (P=0.33 and P=1.0, respectively). More cesarean sections were performed in the dinoprostone group due to failed IOL (P=0.0009). No significant differences in adverse maternal outcome were observed between both study groups, whereas more neonates (12 vs. 6) of the dinoprostone group were admitted to the NICU (P=0.068). Conclusion: This study suggests that misoprostol may have some advantages compared to dinoprostone, including improved efficacy and lower cost of the drug, even in cases of preeclampsia

We have investigated the biological characteristics of an immortalized granulosa cell line (COV434), which may be used to study follicular and oocyte maturation in vitro. Granulosa cell function was defined as consisting of three distinct properties: (i) production of 17β-oestradiol in response to follicle stimulating hormone (FSH); (ii) presence of specific molecular markers of apoptosis enabling the induction of follicular atresia; and (iii) capacity to form intercellular connections with cells surrounding an oocyte. The addition of FSH to the culture medium supplemented with 10% fetal calf serum and 4-androstene-3,17-dione resulted in proliferation of the COV434 granulosa cells and in an increased synthesis of 17β-oestradiol, indicating the presence of the FSH receptor and cytochrome P450 aromatase in these cells. The receptor for luteinizing hormone (LH) was undetectable. Similar expression of various apoptosis-associated genes was found in COV434 granulosa cells and in granulosa cells of patients stimulated with gonadotrophins for in-vitro fertilization, thus indicating that the immortalized COV434 granulosa cells were able to sustain apoptosis. Multiple intercellular connections were formed during co-culture of COV434 granulosa cells with cumulus cells containing an immature oocyte but not with cumulus cells devoid of an oocyte. Detailed morphological analysis of the intercellular connections with scanning electron microscopy and confocal light microscopy demonstrated the presence of long slender structures. It is concluded that the immortalized human granulosa cell line COV434 may be useful for experimental studies on follicular development

BACKGROUND: The preovulatory rise of progesterone is important for ovulation, but both its regulation and its origin are controversial. Three experiments were performed to determine whether follicular phase progesterone arises from the ovary, the adrenal cortex or both. METHODS: The first study was performed in patients scheduled for assisted reproduction, who received a long-acting GnRH agonist either during intake of an oral contraceptive or during the luteal phase of an otherwise untreated menstrual cycle. The second study was also performed during down-regulation with a GnRH agonist: some patients with elevated progesterone levels received dexamethasone (DXM). Others with similarly elevated basal progesterone levels and those with low progesterone levels were not treated with DXM and served as controls. Finally, adrenocorticotrophic hormone (ACTH) tests were performed in normocyclic volunteers both during early and late follicular phase and during intake of a contraceptive pill. RESULTS: During the suppression of endogenous gonadotrophin secretion progesterone levels rose after the administration of ACTH, but not of GnRH. DXM did not prevent the preovulatory rise of the serum progesterone concentration. The ACTH-stimulated concentration of progesterone and of 17α-hydroxyprogesterone were significantly reduced during intake of ethinyl estradiol. CONCLUSIONS: Progesterone arises in the adrenal cortex during most of the follicular phase, whereby its function is modulated by an unknown ovarian factor, which is suppressed by ethinyl estradiol. The source of progesterone shifts towards the ovaries prior to ovulation

Objective: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer. Patients and methods: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for ≥6 months. Results: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). Conclusions: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cancer

Recent studies have suggested that the innate immune system is involved in the pathogenesis of preeclampsia. Its pathogenesis involves neutrophil activation and increased levels of cell-free DNA in the maternal plasma. Activation of neutrophils has recently been shown to induce DNA containing neutrophil extracellular traps (NETs) which trap and kill bacteria. Massive NETs induction by the placentally derived factors (IL-8 and placental micro-debris) and their increased presence in preeclamptic placenta suggest that NETs might be involved in the pathogenesis of preeclampsia. Therefore, increased presence of NETs in preeclampsia may play a role in the deficient placental perfusion associated with this disorder

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P=0.0003, TV: P=0.0009, TSA: P<0.0001; multivariate analyses: MD: P=0.0018, TV: P=0.0109, TSA: P=0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone

Introduction: Iron-deficiency anaemia during pregnancy and postpartum occurs frequently and may lead to severe maternal and foetal complications. New treatment regimens include intravenous iron administration in particular clinical situations. The aim of the study was to determine optimal diagnostic and therapeutic approaches to iron-deficiency anaemia during pregnancy and postpartum. Methods: The evidence from data available from published studies and recommendations regarding diagnosis and treatment were reviewed. As conclusions, recommendations are given by an expert panel. Results: During pregnancy, oral iron therapy is given as first-line treatment. In cases with lack of efficacy, unwarranted side effects or very low haemoglobin values, intravenous iron treatment with iron carboxymaltose is a preferable alternative, although data regarding safety are limited. In the postpartum period, haemoglobin values less than 95g/L are treated ideally by intravenous carboxymaltose, leading to more rapid haemoglobin recovery. Conclusion: New intravenous iron preparations such as iron carboxymaltose have an excellent efficacy, side effect profile and advantages as compared to oral iron preparations for particular clinical indications

Objective: To assess the impact of three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) on maternal-fetal bonding. Study design: Prospective randomized pilot study among low risk women with singleton fetuses in the second and third trimester. Dependent on the randomization pattern, US was commenced either with 2D US or 3D US and the effects were recorded with standardized questionnaires. Results: Sixty patients were included. Although the quality of 2D US, assessed by the examinator, was superior to 3D US, maternal recognition was higher with 3-D US (P=0.004). With 2D US, nulliparous patients had significantly more difficulties visualizing the fetus, than multiparous (P=0.03). However, the maternal preference of 3D US had no significant impact on maternal-fetal bonding. Conclusion: Ultrasound had no significant effect on maternal-fetal bonding. Three-dimensional images may facilitate recognition of the fetus, but 3D US did not have higher impact on maternal-fetal bonding. This finding may be a reason not to consider 3D ultrasound for routine scanning

Purpose: Prolonged first and second stage of labor, isolated prolongation of the second stage, forceps delivery or vacuum extraction, perineal laceration, nulliparity and epidural anesthesia are known risk factors for developing prolonged postpartum urinary retention (PUR). The aim of our study was to analyze number and constellations of these risk factors, in prolonged postpartum urinary retention (PPUR) in our own unit to facilitate the identification of patients at high risk and thus to prevent bladder overdistension by early intervention. Methods: We performed a retrospective analysis of all our cases with PPUR between 2003 and 2008 including variables like age weight, height, body mass index, fetal birth weight and head circumference. Results: The incidence of PPUR at our institution is low being 0.06%. No woman combined all six risk factors. The majority had five risk factors, all had at least four. An isolated prolonged second stage of labor was common to all patients with PPUR. Five women had an epidural anesthesia, three were nulliparous and only two women delivered spontaneously. All but one woman suffered from perineal tears. Interestingly, fetal head circumference was larger than 36cm in four of six cases. Conclusion: In contrast to simple PUR, the prolonged form of PUR could be the result of a cumulative effect of different single risk factors

Objective: Although elective cesarean section (ECS) is the currently recommended modality for delivering women infected with the human immunodeficiency virus (HIV), historical evidence suggests that they are at higher risk of postoperative complications than noninfected women. Those risks have to be carefully balanced against the presumed minimal benefit of ECS, especially in the case of low viral load and high CD4 counts. We therefore compared the incidence and type of post-ECS complications in HIV-infected women, most with low viral loads and high CD4 cell counts, with those in matched noninfected women treated by the same surgical teams. Study design: A Swiss 8-center, prospective, matched case-control study compared minor and major post-ECS complication prevalence, hospital stay and confounding factors (surgeon experience) between HIV-infected and noninfected women. Results: Minor complications in the 53 matched pairs were eightfold more frequent overall in infected women. More frequent specific minor complications were anemia, blood loss and urinary tract infection. Yet the surgeons performing ECS in infected women were more experienced. Complications prolonged hospital stay in infected women. Major complication rates did not significantly differ between the groups. Conclusion: HIV-positive women have a higher risk of post-ECS morbidity, even with high CD4 counts and low viral load. Therefore, the blanket recommendation of ECS in HIV-infected women requires a review