Chorioamnionitis is an acute inflammatory reaction associated with the premature rupture of the fetal membranes. It is caused mainly by invasion of bacteria from the vaginal tract that can penetrate the intact membranes and invade the amnion cavity and the decidua. Tight junctions (TJs) and adherent junctions (AJs) are intercellular junctions crucial for epithelia adhesion and permeability regulation in a wide variety of tissues and organs. Our aim is to investigate if TJ and AJ molecules are involved in human chorioamnionitis. We studied the protein expression (by immunohistochemistry and western blotting) and the mRNA levels (by RT-PCR) of some junction proteins such as Zonula Occludens-1 (ZO-1), occludin, VE-cadherin and β-catenin in fetal membranes from women with chorioamnionitis compared to those membranes derived from idiopathic pregnancies. Western blotting and immunohistochemical data established that occludin expression was decreased in amnion with chorioamnionitis compared to amnion from idiopathic pregnancies. Samples tested for ZO-1, VE-cadherin and β-catenin (proteins and mRNAs) showed no differences between idiopathic and pathological membranes. One of the most relevant results is the decrease of occludin in membranes with chorioamnionitis. Since we have previously demonstrated that some cytokines, particularly elevated in the chorioamnionitis, cause the disruption of TJs in placental villi, we suggest that the decrease of occludin in amnion may be the first change that leads to the rupture of the amniotic membrane in this pathology.

The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options.The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported. Gast © 2015 Editrice

IntroductionAnti-Müllerian hormone (AMH) is a member of the transforming growth factor-β superfamily, playing a role in sexual differentiation and recruitment. Since a correlation exists between AMH serum levels in cord blood and fetal sex, the present study aimed to identify mRNA and protein expression of AMH and AMHRII in placenta and fetal membranes according to fetal sex.MethodsPlacenta and fetal membranes samples (n = 40) were collected from women with singleton uncomplicated pregnancies at term. Identification of AMH protein in placenta and fetal membranes was carried out by immunohistochemistry and AMH and AMHRII protein localization by immunofluorescence, while mRNA expression was assessed by quantitative real-time PCR.ResultAMH and AMHRII mRNAs were expressed by placenta and fetal membranes at term, without any significant difference between males and females. Placental immunostaining showed a syncytial localization of AMH without sex-related differences; while fetal membranes immunostaining was significantly more intense in male than in female fetuses (p < 0,01). Immunofluorescence showed an intense co-localization of AMH and AMHRII in placenta and fetal membranes.DiscussionThe present study for the first time demonstrated that human placenta and fetal membranes expresses and co-localizes AMH and AMHRII. Although no sex-related difference was found for the mRNA expression both in placenta and fetal membranes, a most intense staining for AMH in male fetal membranes supports AMH as a gender specific hormone.

A histologic response of histologic chorioamnionitis (HCA) is defined as an intrauterine inflammatory condition characterized by acute granulocyte infiltration into the fetal-maternal or the fetal tissues. Prevalence of HCA is inversely correlated with gestational age, occurring in 50% of preterm birth and in up to 20% of deliveries at term. Regardless of these standard definitions, understanding HCA is challenging as it reflects a heterogeneous condition. A histologic response of HCA from term placentas often does not correspond to a clinical presentation; in this context, the present review aims to analyze main characteristics of this condition, in particular focusing on mechanisms and birth outcomes.

Objective: Embryo implantation and parturition are recognized as inflammatory events involving endocrine and immune system. NF-kB and MAPK are two transcription factor families involved in inflammation. A possible role of neuroendocrine mechanism in early pregnancy and delivery was proposed for the neuropeptides related to corticotropin releasing hormones (CRH), named Urocortins (Ucns). Experimental and clinical studies support a role for CRH, Ucn, Ucn2 and Ucn3 in the endocrine/immune modulation of inflammation in human trophoblast; however the intracellular mechanisms are not yet recognized.The aim of the present study was to evaluate which of these neuropeptides modulate NF-kB or MAPKs pathways.Study design: In Jeg-3 placental cell line the effect of CRH, Ucn, Ucn2 or Ucn3 on NF-kB and MAPKs pathways were evaluated using Western blot analysis.Results: CRH induced the phosphorylation of MAPK subunits; Ucn2 was able to induce the phosphorylation of both NF-kB and MAPK subunits. Ucn and Ucn3 had no effects on these pathways.Conclusions: These data provide novel information on inflammatory process in trophoblast cells: Ucn2 is a potent pro-inflammatory neuropeptide via NF-kB and MAPK pathways and CRH via MAPK, and CRH and Ucn2 network participates in the inflammatory mechanisms of pregnancy and parturition. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

To evaluate whether placental location, determined by US before delivery, might be related with pregnancy and/or delivery outcome. Patients included in the prospective study (n = 1335) were healthy, carrying singleton pregnancies, admitted for vaginal delivery. Placental position was determined at 37 wks of gestation by US. The primary outcome was the association between placental location and unfavorable delivery outcome, in term of mode and gestational age of delivery, need of induction of labour, duration of active labour, post-partum hemorrhage and manual removal of placenta. The association between placental location and other parameters (age, height, pre-pregnancy BMI, BMI at admission, weight gain and parity) and pregnancy/neonatal outcomes (threatened miscarriage and threatened preterm delivery, vaginal infection, premature rupture of membranes, sex, weight and rate of admission at NICU), were evaluated as secondary outcomes. Among all women, 651 had an anterior placenta (Group A), 592 had a posterior placenta (Group B), 32 had a fundal placenta (Group C), 23 had a right placenta (Group D) and 37 had a left placenta (Group E). Concerning the primary outcome, the rate of PPH was significantly higher in women having an anterior placenta (P = 0.0355); no others differences were shown. Concerning maternal characteristics, Group A patients were more frequently nulliparous than others (p < 0.0001). Newborns of women with anterior placenta had no difference regarding neonatal outcome. In healthy pregnant women anterior located placenta is associated with an increased incidence of PPH, suggesting the relevance of investigating placental location before delivery in order to better manage third stage of labour.

Introduction: Chorioamnionitis is a gestational pathological condition characterized by acute inflammation of the amniochorionic membranes and placentas leading to high concentrations of IL-1 beta, Il-6, Il-8 and TGF-beta in the amniotic fluid. In normal conditions, the permeability of foeto-maternal barrier is due to the assembly and maintenance of different cellular junctional domains.Methods: In the present study, first we aimed to evaluate the protein expression (by immunohistochemistry and western blotting) and mRNA (by real time PCR) levels of the molecular components of tight junctions (Zonula occludens-1 and occludin), and of adherent junctions (VE-cadherin and beta-catenin) in placentas from chorioamnionitis compared to that in normal pregnancies.Results: Western blotting results showed a significant down-regulation of occludin in placentas affected with chorioamnionitis. No differences were detected for the other proteins analysed. We evaluated whether occludin expression was regulated by IL-1 beta, IL-6, IL-8 and TGF-beta by means of in vitro studies using HUVEC cultures and demonstrated a key role of IL-1 beta and TGF-beta in the disappearance of occludin at cellular border. Conclusions. We conclude by suggesting a pivotal role of these two cytokines in facilitating intra-placental infection via para-cellular way due to the disassembly of tight junctions at trophoblastic and endothelial cells in placental tissues. (C) 2014 Elsevier Ltd. All rights reserved.

During pregnancy, the maternal brain drives a series of adaptive mechanisms that are fundamental for allowing fetal growth and development, protecting both mother and fetus from adverse programming and timing of parturition. This neuroendocrine concept is even more complex as fetal brain and placenta also participate as regulators of maternal-placental-fetal physiology. The placenta is now seen as a neuroendocrine organ, acting as a source of several neuroactive factors that may exert their biologic effects either locally or by entering maternal and fetal circulation, thus acting in an autocrine, paracrine, and endocrine manner. A variety of hypothalamic neurohormones (GnRH, GHRH, somatostatin, CRH, oxytocin) are expressed in the placenta. When stress occurs during pregnancy, the maternal, fetal, and placental hypothalamic-pituitary-adrenal (HPA) axes are activated to stimulate a series of responses contributing to maintain physiologic conditions while at the same time avoiding the adverse effects of stress on the mother and offspring. However, when stress is excessive, a number of obstetric complications may occur, such as preterm birth, pre-eclampsia and intrauterine growth restriction, related to an impairment of the placental adaptive response.

Introduction: The aim of the study is to evaluate whether placental location at term is associated with delivery outcome.Methods: A prospective study including 2354 patients with singleton pregnancy at term admitted for vaginal delivery was conducted. Placental position was determined before delivery by ultrasonographic examination performed transabdominally with women in the supine position. Maternal characteristics and delivery outcome such as premature rupture of membranes, induction of labor, mode and gestational age at delivery, indication for cesarean section, duration of the third stage, postpartum hemorrhage (PPH) and manual removal of placenta were correlated with anterior, posterior or fundal placental locations.Results: Among women enrolled: i) 1164 had an anterior placenta, ii) 1087 a posterior placenta, iii) 103 a fundal placenta. Women with anterior placenta showed: i) a higher incidence of induction of labor (p = 0.0001), especially for postdate pregnancies and prolonged prelabor rupture of membranes (p < 0.0001), ii) a higher rate of cesarean section rate for failure to progress in labor (p = 0.02), iii) a prolonged third stage (p = 0.01), iv) a higher incidence of manual removal of placenta (p = 0.003) and a higher rate of PPH in vaginal deliveries (p = 0.02).Discussion: The present study showed the influence of anterior placental location on the course of labor, with a later onset of labor, a higher rate of induction and cesarean section and postpartum complications. The reason for this influence on labor and delivery complications remains to be elucidated. (C) 2014 Elsevier Ltd. All rights reserved.

To estimate the effect of maternal weight gain and BMI on accuracy of estimated fetal weight (EFW) in term pregnancies. A group of 514 singleton term pregnancies were enrolled prospectively at the admission for delivery. Women without 1st trimester dating and with fetal malformations were excluded. Pregravidic and term BMI were collected and weight gain at term was calculated. At admission a fetal biometry (BPD, HC, AC, FL) was recorded and EFW calculated by using Fetal Weight Index (FWI), an informative probability model that reduces human error, enhancing estimation accuracy. EFW accuracy was defined as the absolute error (AE) (absolute value of EFW minus BW) and absolute percent error (AE%) (absolute error divided by BW multiplied by 100). Unpaired t-test, Mann-Whitney U test, Fisher's exact test and Kruskal-Wallis test were used for statistical analysis. 501 consecutive patients met the inclusion criteria. The mean pregravidic and term BMI was 23 ± 4.1 kg/m2 and 28 ± 3.9 kg/m2, respectively. The mean maternal weight gain at term was 13 ± 4.2. Fetal biometry was performed within 6 days from delivery. The mean EFW was 3323 ± 439 gr while the mean BW was 3361 ± 509 gr. Median AE% was 6.5 ± 4.9%. Pregravidic and term BMI was not associated with AE and AE% of EFW, in terms of under- or over-estimation. No association was shown between AE and AE% and weight gain. AE and AE% showed no statistically significant difference in patients with BMI at term more or less than 30. In the subgroup of 45 patients who delivered infants >4,000 g, BMI was not significantly associated with AE and AE%. Our results show that EFW using FWI in term pregnancies is not significantly affected by maternal BMI and weight gain. Thanks to FWI, each operator knows in real-time the percentage of accuracy of each biometric parameter detected, thus allowing the re-evaluation and the correction of inaccurate data. Reducing human error by FWI, the impact of maternal BMI on ultrasound accuracy seems to be minimal.

The purpose of the study was to investigate urocortin (Ucn)2 involvement in placental and myometrial inflammatory pathways associated with parturition by evaluating: 1) Ucn2 and its receptor, CRH-receptor type 2 (CRH-R2), expression in laboring/nonlaboring human gestational tissues and in mouse utero-placental tissues approaching delivery; and 2) Ucn2 effect on myometrial contractility and on the expression of inflammatory mediators (prostaglandin F2α receptor and cytokines) and regulation of Ucn2 by TNF-α in cultured myometrial cell line. Placenta (n = 16), fetal membranes (n = 16), and myometrium (n = 22) were obtained from healthy pregnant women delivering at term by vaginal/elective caesarean delivery and from timed-pregnant mice on days 16-19. Expression of Ucn2/CRH-R2 in human/mouse tissues and inflammatory mediators in myometrial cell lines were measured by RT-PCR or ELISA, mouse Ucn2/CRH-R2 protein localization by immunohistochemistry. Ucn2 but not CRH-R2 was up-regulated (P < .05) in all human tissues in labor (compared with before labor) and increased significantly (P < .01) in mouse placenta approaching delivery. Ucn2 was up-regulated by TNF-α via nuclear factor-κB (NF-kB) in myometrium cell lines (P < .05 or P < .01 on the basis of treatment doses) and increased proinflammatory mediators and prostaglandin F (PGF2α) receptor expression (P < .05) via CRH-R2, without a direct effect on contractility. Placental and myometrial Ucn2 may play a role in the endocrine-inflammatory processes of parturition, representing a potential target for treating inflammation-induced obstetric complications.

Objective: To determine delivery outcome in women undergoing induction of labor for postdate pregnancy in relation to fetal gender. Study Design: A total of 365 nulliparous and 127 multiparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. Clinical characteristics and delivery outcome were analyzed in relation to fetal gender. Results: Women carrying male fetuses showed higher rate of caesarean section than those carrying females, in both nulliparous and multiparous women. Moreover, women carrying male fetuses presented more frequently with (i) interval between induction of labor and delivery >24 hours (P < .0002); (ii) augmentation of labor after cervical ripening (P < .0391); (iii) meconium-stained liquor (P< .0126); and (iv) higher neonatal weight (P < .0011) than those carrying females. Conclusion: Male fetuses are more likely to be associated with higher rates of cesarean section. In maternal fetal medicine, gender differences may add prognostic information on the delivery outcome in women induced for postdate pregnancy.

OBJECTIVE:To evaluate whether maternal weight and body mass index (BMI) and their increase throughout pregnancy are associated with the response to labor induction in postdate pregnancies.METHODS:A total of 376 nulliparous women carrying singleton postdate pregnancies with unfavorable cervix were enrolled. We considered as primary outcome vaginal delivery within 24 h after induction, and outcomes were divided into responders (n = 258) and non-responders (n = 107) to the induction of labor to perform the statistical analyses.RESULTS:In the total population of study, women who successfully delivered within 24 h differed significantly from the remaining patients in terms of maternal weight gain (p = 0.009) and BMI increase (p = 0.02) during pregnancy. In addition, males were significantly more (p = 0.005) than females among newborns of women not responding to induction of labor. In the multivariate analysis, maternal weight gain and fetal sex significantly influenced the induction response. The occurrence of a failed induction of labor was more likely in patients presenting a greater maternal weight gain (cut-off 12 kg) and male fetus.CONCLUSION:Weight gain over 12 kg regardless of pre-pregnancy weight and male fetal gender are two novel potential risk factors for the prediction of failure to induction of labor in postdate pregnancy.

Objective: The aim of this study was to investigate the rate of the different histological chorioamnionitis (HCA) grade in relation to the gestational age in term and preterm delivery.Methods: Three hundred and ninety-two women with singleton pregnancy with spontaneous onset of labor either prematurely or at term, with histologic diagnosis of HCA, were enrolled. Placentas were classified as: deciduitis and/or histologic chorioamnionitis within the membranes (HCA1); amnionitis or inflammation of the chorionic plate without funisitis (HCA2); and histologic chorioamnionitis with funisitis (HCA3). Microbiological culture was performed on both placental and fetal membrane samples.Results: HCA1 was more frequent in women delivering at term than in preterm (p<0.001). HCA2 was more represented in women delivering between 32 and 36 weeks (p<0.001) and HCA3 occurred more frequently in those delivering within 32 weeks (p<0.001). The positive bacterial culture was higher (p = 0.008) in presence of HCA3 in comparison with HCA1 and HCA2.Conclusions: This study showed a significantly different distribution of HCA grades in relation to gestational age at delivery. HCA may represent the expression of different subtending etiologies and may also reflect specific immune competence of gestational tissues at different gestational ages, strengthening as pregnancy advances.

OBJECTIVE:The aim of the present study was to evaluate: i) the rate of histologic chorioamnionitis in relation to the onset of labor and mode of delivery; ii) influence of clinical parameters on the risk of histologic chorioamnionitis in laboring women; iii) neonatal outcome in relation to histologic chorioamnionitis.METHODS:A cohort study was conducted on 395 healthy women at term, with singleton uneventful pregnancy, of which 195 with spontaneous onset of labor and 200 with elective cesarean section. All placentas, collected after delivery, were examined for the diagnosis of histologic chorioamnionitis. Mode of delivery, presence of bacterial infection of placenta and membranes, maternal clinical parameters and neonatal outcome were recorded.RESULTS:The rate of histologic chorioamnionitis in women with spontaneous onset of labor was significantly higher than in those experiencing elective cesarean section (28.7% vs. 11.5%). Nulliparity and the duration of labor were independent variables associated with acute histologic chorioamnionitis. The presence of histologic chorioamnionitis did not affect neonatal outcome.CONCLUSIONS:The present study showed a highest rate of histological chorionamniositis in women delivering after spontaneous onset of term labor, although the mode of delivery either vaginally or by emergency cesarean section was not influenced by the presence of this pathological condition.