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Aim To evaluate low back pain (LBP) incidence and impact throughout pregnancy in terms of women’s well-being and delivery outcomes. Material and methods Cross-sectional prospective study conducted on singleton pregnancies at ≥37th gestational age admitted for delivery. Localization of LBP, intensity and frequency as well as derived functional disability status were assessed with a self-reported questionnaire. Main delivery outcomes including mode of delivery, and maternal or neonatal complications were recorded. Results A total of 229 women participated in the study. LBP prevalence amounted to 55.9%, with the pain already present before pregnancy in 14.0% of the cases. The pain was mostly localized in the lower back (40.6%), symphysis (23.3%), and coccyx (20.5%). Both the frequency and intensity of pain gradually increased significantly during pregnancy, reaching 20 days/month (IQR=10–30) and 6/10 points (IQR=5–8) on a visual analog scale in the 3rd trimester (p Conclusions LBP is a common issue in pregnant women, accounting for increasing morbidity and invalidity, and leading to an increased cesarean section risk during labor.

Efforts to use traditional native tissue strategies and reduce the use of meshes have been made in several countries. Combining native tissue repair with sufficient mesh applied apical repair might provide a means of effective treatment. The study group did perform and publish a randomized trial focusing on the combination of traditional native tissue repair with pectopexy or sacrocolpopexy and observed no severe or hitherto unknown risks for patients (No&eacute, G.K. J Endourol 2015, 29(2):210&ndash, 5.). The short-term follow-up of this international multicenter study carried out now is presented in this article. Material and Methods: Eleven clinics and 13 surgeons in four European counties participated in the trial. In order to ensure a standardized approach and obtain comparable data, all surgeons were obliged to follow a standardized approach for pectopexy, focusing on the area of fixation and the use of a prefabricated mesh (PVDF PRP 3 &times, 15 Dynamesh). The mesh was solely used for apical repair. All other clinically relevant defects were treated with native tissue repair. Colposuspension or TVT were used for the treatment of incontinence. Data were collected independently for 14 months on a secured server, 501 surgeries were registered and evaluated. Two hundred and sixty-four patients out of 479 (55.1%) returned for the physical examination and interview after 12&ndash, 18 months. Main Outcome and Results: The mean duration of follow-up was 15 months. The overall success of apical repair was rated positively by 96.9%, and the satisfaction score was rated positively by 95.5%. A positive general recommendation was expressed by 95.1% of patients. Pelvic pressure was reduced in 95.2%, pain in 98.0%, and urgency in 86.0% of patients. No major complications, mesh exposure, or mesh complication occurred during the follow-up period. Conclusion: In clinical routine, pectopexy and concomitant surgery, mainly using native tissue approaches, resulted in high satisfaction rates and favorable clinical findings. The procedure may also be recommended for use by general urogynecological practitioners with experience in laparoscopy.

Objective: To reduce mesh use for prolapse repair, practice has shifted towards traditional native tissue. Combining native tissue repair with sufficient apical repair could allow effective treatment. Pectopexy showed in a randomized trial focusing on combining traditional native tissue repair with pectopexy or sacrocolpopexy no association with new risks for patients. The short follow-up of this international multicenter study is presented in this article. Design, Setting, and Population: Eleven clinics and 13 surgeons in four European counties participated in the study. All surgeons committed to using a strict standard for pectopexy, using a pre-tailored mesh (PVDF PRP 3×15 Dynamesh solely for apical repair. Methode: Data were independently collected for 14 months on a secured server; 501 surgeries were documented and evaluated and 264 (52.7%) patients returned for physical examination for follow-up. Main Outcome and Results: The mean follow-up time was 15 months, and the overall success rate for apical repair was 96.9%. A satisfaction score was positively rated in 95.5% of the patients. A positive general recommendation was provided by 95.1% of the patients. Pelvic pressure was reduced in 95.2%, pain was reduced in 98.0%, and urgency was reduced in 86.0%.No major de novo problems occurred in the follow-up. Conclusion: Clinical routine pectopexy and concomitant surgery, mainly using native tissue approaches, resulted in high satisfaction rates and good clinical findings. The procedure can also be recommended for general use by general uro-gynecological practitioners with experience in laparoscopy. Funding: FEG Textieltechnik; Aachen Keywords: prolapse; pelvic floor; laparoscopy; native tissue, pectopexy

The technique of laparoscopic pectopexy was published in 2010. A subsequent randomized trial focused on pectopexy versus sacropexy revealed no new risks for patients and significant advantages in terms of operating time and de novo defecation disorders compared to sacrocolpopexy. The present international multicenter trial was performed to evaluate the applicability of the technique in clinical routine. Material and Method Eleven clinics and 13 surgeons in four European counties participated in the trial. To ensure a standardized approach and obtain comparable data, all surgeons followed the same rules in placing the apical tape, no further mesh was used. Data were collected for 14 months on a secured server; 501 surgeries were documented and evaluated. Results Patients treated at the leading center (2 surgeons) contributed 44 % of the patient population. We made a distinction between high-volume (48–135 surgeries annually) (n = 4), intermediate-volume (28–37 surgeries annually) (n = 4), and low-volume (7–22 surgeries annually) (n = 5) surgeons. 97.3 % of the patients (n = 501) had delivered children; 5.6 % had had a Caesarian section. 29.7 % of the patients had undergone a hysterectomy. The operating time for pectopexy was less than 60 min in 79 % of cases. The procedures were completed in less than 159 min in 71 % of cases. Severe complications (n = 5) included four cases of organ damage (related to concomitant surgeries or adhesions) and one case of relevant bleeding. De novo incontinence was registered in two cases and voiding dysfunction in three. No intestinal obstruction or defecation disorder was observed. Two complicated infections were noted. Urinary infection occurred in 2 % of patients. Conclusion In clinical routine severe complications occurred in 1 %. The latter were unrelated to pectopexy, but occurred due to concomitant procedures or adhesions. The overall operating time as well as the operating time for pectopexy were similar to those reported in published studies on sacrocolpopexy.

Infections during pregnancy can adversely affect the development of the fetal brain. This may contribute to disease processes such as schizophrenia in later life. Changes in the (cyto-) architecture of the anterior cingulate cortex (ACC), particularly in GABA-ergic interneurons, play a role in the pathogenesis of schizophrenia. We hypothesized that exposure to infection during pregnancy could result in cyto-architectural changes in the fetal ACC, similar to the pathogenesis seen in schizophrenia. Fetal sheep of 110 days GA (term=150 days GA) received an intravenous injection of 100 ng or 500 ng lipopolysaccharide (LPS) or saline as control. After delivery at 113 days GA, the cyto-architecture of the cingulate cortex (CC) was examined by immunohistochemistry. High dose LPS exposure resulted in a decreased density of GFAP-, calbindin D-28K- and parvalbumin-immunoreactive cells in the CC. In addition, these cells and calretinin-immunoreactive cells showed a changed morphology with reduced cell processes. This study provides further evidence that intra-uterine endotoxemia can induce changes in the fetal brain which correspond with changes seen in schizophrenia.

Exposure of the fetus to antenatal inflammation can occur from chorioamnionitis, which may progress to a fetal inflammatory response syndrome (FIRS) and to fetal sepsis. We tested whether the fetal myocardium responded to systemic Gram-negative endotoxinaemia. We hypothesized that the myocardium would respond to inflammation by changes in hypoxia-inducible factor-a (HIF-1 alpha), inducible NO-synthase (iNOS), Toll-like receptors 2 and 4 (TLR2 and TLR4), IL-6, and phosphorylated signal transducer and activator of transcription-3 (pSTAT3). To model systemic endotoxinaemia, fetal sheep were exposed to Gram-negative endotoxin or saline iv. 3 d before preterm delivery at 113 d of gestation (term = 147 d). All endotoxin-exposed animals developed cardiac dysfunction within these 72 h. Cardiac mRNA and protein levels of HIF-1 alpha and TLR2 and TLR4 mRNA increased, whereas STAT3 phosphorylation decreased significantly. IL-6 and iNOS mRNA remained unchanged. Fetal systemic endotoxinaemia induced myocardial inflammation by activating TLR2 and 4. The following cardiac dysfunction seems not to be mediated via cardiac iNOS. (Pediatr Res 70: 242-246, 2011)

We evaluated the impact of chorioamnionitis on the intrapartal EEG delta frequency in the non-anesthetized preterm sheep. 10 mg intra-amniotic LPS or saline were given 2 or 14 days before preterm birth at gestational day 125. Lambs were delivered by Caesarean section under local anesthesia. A 5-minute EEG depicted delta activity and amplitude, and the relationship between EEG delta activity and both the white matter (WM) and cortical microglial activation and apoptosis was analyzed. EEG delta activity was increased significantly in the 14-day LPS preterm fetuses compared to both preterm control and 2-day LPS animals (p less than 0.05). No differences were seen between controls and the 2-day LPS fetuses. A direct association was demonstrated between EEG delta activity and both cortical microglial activation (r = 0,645, p = 0,024) and apoptosis (r = 0,580, p = 0,048), and between delta and WM activated microglia (r = 0,742, p = 0,006) and apoptosis (r = 0,777, p = 0,003). This study is the first to show a relationship between brain dysfunction and chorioamnionitis-related injury at birth.

The challenge in developing liposomes to be used in active drug targeting is to design a method that can be used for modifying liposomal membranes that is applicable for a number of different specific ligands. In this study, the post insertion technique was used with activated sterol-PEG(1300) anchors and was evaluated with regard to its effectiveness in active targeting in vitro. The key advantage of these anchors is that the insertion step into the liposomal membrane takes place at room temperature and is very fast.For in vitro experiments, neuroblastoma cell lines overexpressing GD2 antigen on their surface as a target structure were chosen. This allowed the use of anti-GD2 antibodies coupled to the liposomal surface for testing of specific binding. These modified liposomes were labelled with rhodamine-PE and their cellular association was analyzed by flow cytometry.It was shown that the activated sterol-PEG(1300) anchors allow specific and significant interactions of the modified liposomes with GD2 positive cells.Coupling using sterol-PEG(1300) anchors is both simple and rapid. It is reproducible and applicable for all ligands bearing amino groups. This method demonstrates the advantage of a ready-to-use system for the modification of pre-formed liposomes with different ligands.

Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.

Background: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. Objective: To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. Methods: In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H2O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. Results: Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. Conclusion: In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.

Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis. Chorioamnionitis was induced at different gestational ages (GA). Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d) inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO) donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase. Our results indicate that the distribution of the tight junctional protein ZO-1, the immune defence and vascular function are immature at low GA and are further compromised by endotoxin-induced chorioamnionitis. This study suggests that both prematurity and inflammation in utero disturb fetal gut development, potentially predisposing to postnatal intestinal pathology.

The sheep placenta is an often used model in placental research. Uterine epithelium and trophoblast of this synepitheliochorial placenta form a complex, intensely interdigitating epithelial barrier separating maternal and fetal organisms. The close topographical relation and additionally the presence of hybrid syncytia formed by focal fusion of both epithelia hamper identification of the various cellular constituents. Therefore we aimed to find a specific immunohistochemical marker differentiating between the fetomaternal syncytial plaques and trophoblast. A monoclonal antibody directed against type II cytokeratins strongly stained unicellular trophoblast. The syncytial plaques were only weakly stained while binucleate trophoblast remained unstained. This antibody proved to be a useful tool for easy histological orientation in the sheep placenta. In combination with other antibodies in double immunohistochemistry it facilitates exact localization of antigens.

Objectives Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. Study design Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107 ± 1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n = 8) or saline (control; n = 6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid–base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. Results Fetal tachycardia and hypertension were induced transiently during the first 12 h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. Conclusions Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.

Brain damage around birth may cause lifelong neurodevelopmental deficits. We examined the therapeutic potential of human umbilical cord blood-derived mononuclear cells containing multipotent stem cells to facilitate motor recovery after cerebral hypoxic-ischemic damage in neonatal rats. Left carotid artery ligation followed by 8% O(2) inhalation for 80 min was performed on postnatal d 7, succeeded by intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells on postnatal d 8 in a sham-controlled design. Histologic and immunohistochemical analysis on postnatal d 21 revealed that neonates developed severe cerebral damage after the hypoxic-ischemic insult. These animals also suffered from contralateral spastic paresis, as evidenced by their locomotor behavior. After transplantation of human umbilical cord blood-derived mononuclear cells, spastic paresis was largely alleviated, resulting in a normal walking behavior. This "therapeutic" effect was accompanied by the fact that mononuclear cells had entered the brain and were incorporated around the lesion without obvious signs of transdifferentiation. This study demonstrates that intraperitoneal transplantation of human umbilical cord blood-derived mononuclear cells in a rat model of perinatal brain damage leads to both incorporation of these cells in the lesioned brain area and to an alleviation of the neurologic effects of cerebral palsy as assessed by footprint and walking pattern analysis.

Objective We quantified the impact of chorioamnionitis on both the white and gray matter structures of the preterm ovine central nervous system (CNS). Study Design The CNS was studied at 125 days of gestation, either 2 or 14 days after the intraamniotic administration of 10 mg of lipopolysaccharide (LPS) ( Escherichia coli ) or saline. Apoptotic cells and cell types were analyzed in the brain, cerebellum, and spinal cord using flow cytometry. Results Apoptosis and microglial activation increased in all regions with prolonged exposure to LPS-induced chorioamnionitis. Astrocytes were increased in the brain and cerebellum of LPS-exposed fetuses but not in the spinal cord. Mature oligodendrocytes decreased in the cerebral and cerebellar white matter, the cerebral cortex, caudate putamen, and hippocampus 14 days after LPS. Neurons in the cerebral cortex, hippocampus, and substantia nigra were reduced 14 days after LPS. Conclusion Fetal inflammation globally but differentially affected the CNS depending on the maturational stage of the brain region.

Background Antenatal pulmonary inflammation is associated with reduced risk for respiratory distress syndrome but with an increased risk for bronchopulmonary dysplasia (BPD) with impaired alveogenesis. Objective We hypothesized that fetal systemic inflammation induced by intravenous (IV) lipopolysaccharide (LPS) would affect lung development in utero. Study Design Twenty-one fetal sheep were instrumented (107 days gestational age). Control fetuses received saline (N = 12) and 9 in the study group received 100 ng of LPS IV 3 days after surgery. Animals were assessed for lung maturation and structure after 3 (N = 5) and 7 (N = 4) days. Results Interleukin-6 concentration increased in the bronchoalveolar lavage more than 40-fold 3 days after LPS IV. Processing of pro-surfactant protein (SP)-B to mature SP-B and increased SP-B concentrations were shown 7 days after LPS IV. Deposition of elastin fibers at sites of septation was disturbed within 3 days after LPS IV. Conclusion Lung maturation and disturbed lung structure occurred after short-term exposure to fetal inflammation and suggests new targeted therapies for BPD.