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Objective: To compare the neonatal and maternal outcomes as well as the mode of delivery of intended vaginal breech deliveries in women with a prior cesarean section to primiparous patients., Study Design: The prospective monocenter cohort study was conducted among 604 women who presented for an intended vaginal singleton breech delivery at term between January 2007 and December 2016., Results: Out of 37 women with a prior cesarean 19 had a successful vaginal delivery. 344 of 567 primiparous women had a successful vaginal delivery. Neonatal morbidity and mortality as well as maternal outcome were not significantly different in successful vaginal deliveries of women with prior cesarean compared to primiparous patients. The cesarean section rate was not significantly higher in the group of women with a prior cesarean (49%) compared to the group of primipara (39%)., Conclusion: A prior cesarean should not be taken as an exclusion criterion for a planned vaginal delivery out of a breech presentation at term. Large multicenter, case-controlled studies are necessary to implement international guidelines., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The clinical management of breech presentations at term is still a controversially discussed issue among clinicians. Clear predictive criteria for planned vaginal breech deliveries are desperately needed to prevent adverse fetal and maternal outcomes and to reduce elective cesarean section rates. The green-top guideline considers an estimated birth weight of 3.8 kg or more an indication to plan a cesarean section despite the lack of respective evidence., Objective: To compare maternal and neonatal outcome of vaginal intended breech deliveries of births with children with a birth weight of 2.5 kg- 3.79 kg and children with a birth weight of 3.8 kg and more., Design: Prospective cohort study., Sample: All vaginal intended deliveries out of a breech position of newborns weighing between 2.5 kg and 4.5 kg at the Obstetrics department at Goethe University Hospital Frankfurt from January 2004 until December 2016., Methods: Neonatal and maternal outcome of a light weight group (LWG) (< 3.8 kg) was compared to and a high weight group (HWG) (≥ 3.8 kg) using Pearson's Chi Square test and Fishers exact test. A logistic regression analysis was performed to detect an association between cesarean section rates, fetal outcome and the birth weight., Results: No difference in neonatal morbidity was detected between the HWG (1.8%, n = 166) and the LWG (2.6%, n = 888). Cesarean section rate was significantly higher in the HWG with 45.2% in comparison to 28.8% in the LWG with an odds ratio of 1.57 (95% CI 1.29-1.91, p<0.0001). In vaginal deliveries, a high birth weight was not associated with an increased risk of maternal birth injuries (LWG in vaginal deliveries: 74.3%, HWG in vaginal deliveries: 73.6%; p = 0.887; OR = 1.9 (95% CI 0.9-1.1))., Conclusion: A fetal weight above 3.79 kg does not predict increased maternal or infant morbidity after delivery from breech presentation at term. Neither the literature nor our analyses document evidence for threshold of estimated birth weight that is associated with maternal and/or infant morbidity. However, patients should be informed about an increased likelihood of cesarean sections during labor when attempting vaginal birth from breech position at term in order to reach an informed shared decision concerning the birth strategy. Further investigations in multi center settings are needed to advance international guidelines on vaginal breech deliveries in the context of estimated birth weight and its impact on perinatal outcome., Competing Interests: The authors have declared that no competing interests exist.

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings., (Copyright © 2016 by the American Society of Nephrology.)

Aims: Preeclampsia (PE) is considered a uniformly progressive disease, however, it shows a different pattern of clinical progression in patients with early (<34 weeks) or late (≥ 34 weeks) onset of the disease. Angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) are closely related to the clinical course of PE. We evaluated sFlt-1 and PlGF levels in the clinical course of PE in women admitted with a diagnosis of PE at different gestational ages., Methods: This retrospective study included 34 patients with PE, of which 11 patients had HELLP syndrome (over a period of 3 years). Serial measurements of sFlt-1 and PlGF were completed from admission until delivery. Values are presented as mean ± standard deviation., Results: Mean gestational age of admission among women with early onset PE was significantly lower, at 29 ± 3 weeks compared to 37±1 weeks among patients with late onset disease. Mean prolongation of pregnancy was 6 days, which was similar within the two groups. Compared to women with late onset PE, women with early-onset PE had a greater increase in sFlt-1 (11% vs. 3% per day, P<0.05), greater decrease in PlGF levels (21% vs. 10% per day, P=0.30), resulting in a much higher increase in sFlt-1/PlGF ratio (23% vs. 8% per day, P<0.05). Patients with HELLP syndrome showed comparable progression patterns., Conclusion: In a similar way to the progressively worsening clinical course observed in women with early onset PE, there were changes in the angiogenic profile that leads to a more anti-angiogenic state in these women with each passing day. These findings may have implications in identification of the women for appropriate patient management and possible future therapies based on the reduction of sFlt-1 levels.

Background: Preeclampsia (PE) is a serious cardiovascular complication in pregnancy, which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Fibroblast growth factor (FGF)-21 was recently introduced as a novel adipokine improving glucose metabolism in vitro and in vivo., Material and Methods: We investigated serum FGF-21 levels in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of FGF-21 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was elucidated in all individuals., Results: Median maternal FGF-21 serum concentrations adjusted for body mass index and gestational age at blood sampling were significantly, almost 3-fold increased in PE patients (309.6 ng/l) as compared to healthy, age-matched pregnant women (105.2 ng/l) (p<0.001). Furthermore, FGF-21 concentrations were independently and positively correlated with triglycerides whereas an independent and negative association was observed with glomerular filtration rate and low density lipoprotein (LDL) cholesterol in pregnant women. Moreover, FGF-21 serum levels significantly decreased in former PE patients 6 months after pregnancy approaching levels found in control patients., Conclusions: Maternal FGF-21 serum concentrations are significantly increased in PE during pregnancy. Furthermore, triglycerides, glomerular filtration rate, and LDL cholesterol are independent predictors of circulating FGF-21 in pregnant women., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Preeclampsia (PE) contributes to maternal and fetal morbidity and mortality worldwide. Moreover, it is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, growth arrest specific protein (Gas) 6 has been introduced as a novel metabolic risk factor with anti-angiogenic, pro-atherogenic, and pro-adipogenic properties. In the current study, we investigated serum concentrations of Gas6 in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of Gas6 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was assessed in all individuals. Median maternal Gas6 serum levels adjusted for body mass index and gestational age at blood sampling were significantly increased in PE patients (5.7 μg/l) as compared to healthy, age-matched pregnant women (4.6 μg/l) (p<0.05). Furthermore, Gas6 concentrations positively correlated with blood pressure, creatinine, free fatty acids, C-reactive protein, leptin, and adiponectin during pregnancy. Moreover, leptin and adiponectin remained independently associated with Gas6 levels in multivariate analysis. Gas6 serum levels 6 months after pregnancy were not significantly different between former PE and control patients. Taken together, maternal Gas6 serum concentrations are significantly increased in PE during pregnancy. Furthermore, the adipokines leptin and adiponectin are independent predictors of circulating Gas6 in pregnant women., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: Preeclampsia (PE), a serious multisystem disorder in pregnancy, is a leading cause of maternal and fetal morbidity and mortality worldwide and angiogenic factors like sFlt-1 and PlGF are closely related to the clinical course of preeclampsia., Objectives: We wondered, if these factors and the sFlt-1/PlGF ratio are a tool to differentiate the clinical progression pattern between early and late-onset PE and HELLP syndrome., Methods: This retrospective study included 30 patients with PE out of which 7 patients had HELLP syndrome. Early onset PE was defined as patients with gestational age <34 weeks. Serial measurements of sFlt-1 and PlGF using the automated Elecsys platform (Roche®) were done from admission until delivery., Results: Early-onset PE is characterized by an increase of sFlt-1 of 66% leading to an 137% increase of the sFlt-1/PlGF ratio. Late-onset PE shows a slower progression with an increase of the sFlt-1/PlGF ratio of only 39%. Patients with HELLP syndrome show comparable progression pattern., Conclusion: Angiogenic factors characterize PE and HELLP syndrome as continuously progressive diseases with a uniform development towards an antiangiogenic state. Early-onset subtypes show a more aggressive progression with a faster sFlt-1 increase., (Copyright © 2012. Published by Elsevier B.V.)

Background: Preeclampsia (PE) is associated with facets of the metabolic syndrome and an increased future metabolic and cardiovascular risk for mother and newborn. Recently, zinc-α2-glycoprotein (ZAG) has been proposed as a new adipokine involved in the pathogenesis of obesity., Aim: In the current study, we investigated ZAG serum levels in PE patients as compared to healthy gestational age-matched controls., Subjects and Methods: We quantified serum concentrations of ZAG in patients with PE (no.=37) as compared to healthy gestational age-matched controls (no.=37) by enzyme-linked immunosorbent assay. Furthermore, association of this adipokine with renal function, glucose and lipid metabolism, as well as inflammation was studied., Results: Median serum ZAG levels were 1.4-fold higher in PE patients (58.8 mg/l) as compared to controls (41.9 mg/l) (p<0.01). Furthermore, circulating ZAG was positively correlated to systolic and diastolic blood pressure, creatinine, triglycerides, and leptin in univariate analyses. In multiple regression analysis, creatinine remained independently associated with ZAG., Conclusions: We demonstrate that maternal ZAG serum concentrations are significantly increased in PE. Furthermore, renal function is an independent predictor of circulating ZAG.

Background: Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm (<32 weeks) preeclampsia., Methods and Results: We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27+4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth., Conclusions: This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.

Light- and electron-microscopie studies were performed in glia cells and neurons of the cerebellum of 12-day-old rats until 48 following intraperitoneal application of 8 mg/kg 6-aminonicotinamide (6-AN), an antimetabolite of nicotinamide that inhibits the oxidative pentose-phosphate pathway. Particularly sensitive were the neuroblasts of the external granular layer. The migration of the neuroblasts was clearly reduced. Parts of the internal granular layer were damaged, while the Purkinje cells and astrocytes remained unchanged. Oligodendrocytes and astrocytes showed vacuolar degeneration. Swelling of the myelin sheath occurred in the form of a status spongiosus. 48 h after 6-AN injection some mitoses and phagocytic cells were found in the internal granular layer.

6-Aminonicotinamide (6-AN), an antimetabolite of nicotinamide, damages the astrocytes and oligodendrocytes through a blockade of the pentose phosphate pathway. Both types of glia cells become hydropic. A third type of glia cell, described by VAUGHN and PETERS, the multipotential glia, is affected to a lesser extent. These cells phagocytize and form pseudopodia after treatment with 6-AN. Thus the multipotential glia cells are 'marked' by the action of 6-AN, since they are obviously less dependent on the pentose phosphate pathway in the carbohydrate metabolism.

A total of 3406 brains were used to determine the relationship between length of body and weight of brain, which at a correlation coefficient of approximately 0.3 are not very close. Individual results are in good agreement with those reported in a similar paper by Polish authors. It is suggested that additional influential factors be included in such considerations.