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Purpose To determine the validity of Intrapartum ultrasound (IPUS), and particularly the angle of progression (AOP), in predicting delivery mode when measured in real-life clinical practice among women with protracted second stages of labor. Methods Using electronic medical records, nulliparous women with a second stage of labor of ≥ 3hours ("prolonged") and a documented AOP measurement during the second stage were identified. The ability of a single AOP measurement in "prolonged" second stage to predict a vaginal delivery (VD) was assessed. Fetal head descend, measured by AOP change/hour (calculated from serial measurements) was compared between women who delivered vaginally and those who had a cesarean delivery (CD) for arrest of descent. Results Of the 191 women who met the inclusion criteria, 62 (32.5%) delivered spontaneously, 96 (50.2%) had a vacuum extraction (VE) and 33 (17.3%) had a CD. The mean AOP was wider among women who had VD (spontaneous or VE) compared to those who had CD (153º±19 vs. 133º±17, p

There are limited data on follow-up, treatment, and maternal and fetal outcomes in women with prediabetes before or at the beginning of pregnancy. The aim of this study was to comprehensively characterize women with prediabetes compared to women with type 2 diabetes mellitus. This was a retrospective cohort data from a single medical center treating women with pregestational prediabetes mellitus (PDM). Women were compared to pregestational overt type 2 diabetes mellitus (T2DM). Data were collected from 120 women in the PDM group and 86 women in the T2DM group. Baseline characteristics were comparable, albeit women in the PDM group arrived at medical attention significantly later, 55% after 15 weeks gestation. Women with PDM needed significantly less treatment to achieve glycemic control and glycated hemoglobin remained lower throughout pregnancy. Maternal and fetal outcomes were similar between groups, although significantly higher rates of macrosomia and neonatal jaundice were observed in the T2DM group. The lack of clear guidelines causes a delay in the first prenatal visit of women with PDM. Comparable pregnancy outcomes may tip the balance toward acceptance of early treatment. Establishing clear guidelines will enable primary caregivers to refer prediabetic women sooner for lifestyle modifications and treatment if needed.

Assessment of labor progress via digital examination is considered the standard of care in most delivery rooms. However, this method can be stressful, painful, and imprecise, and multiple examinations increase the risk for chorioamnionitis. Intrapartum ultrasound was found to be an objective, noninvasive tool to monitor labor progression.This study aimed to investigate whether, among nulliparous women, the use of intrapartum ultrasound can reduce the rate of intrapartum fever by reducing the number of digital examinations.This was a prospective, randomized controlled trial in term nulliparas admitted with prelabor rupture of membranes, induction of labor, or in latent phase of labor with a cervical dilation of4 cm. Women were randomized into 1 of the following 2 arms: (1) labor progress assessed by ultrasound, avoiding digital examinations as much as possible; and (2) control group in which labor progression was assessed according to the regular protocol. Before the study, all labor ward physicians underwent training in intrapartum ultrasound.A total of 90 women were randomized to the ultrasound group and 92 were randomized to the control group. When compared with the control group, the ultrasound group had significantly lower rates of intrapartum fever (11.1% vs 26.1%; P=.01), clinical chorioamnionitis (3.3% vs 16.5%; P.01), and histologic chorioamnionitis (2.2% vs 9.8%; P=.03). The median number of digital examinations was significantly lower in the ultrasound group (5; interquartile range, 4-6) than in the control group (8; interquartile range, 6-10; P.01). The median number of digital examinations per hour in the ultrasound group was significantly lower than in the control group (0.2 vs 0.4; P.01). The induction rates, time from admission to delivery, mode of delivery, Apgar score at 5 minutes, and neonatal intensive care unit admission rates did not differ significantly between the groups.The use of intrapartum ultrasound lessens the total number of digital examinations needed to be performed during labor and, consequently, the incidence of intrapartum fever and chorioamnionitis are reduced. No adverse effects on labor progression and short-term maternal or neonatal outcomes were noted.

Adrenal nonadenomatous tumors (NAT) first identified during pregnancy are very rare and pose a diagnostic and therapeutic dilemma with significant risks for the mother and fetus. The aim of this study is to report a case of a large adrenal NAT identified in pregnancy and literature review. A literature search was conducted, and data were summarized. A 37-year-old primigravida woman, with a history of melanoma, excised 12 years before presentation without recurrence, presented at 35 weeks gestation due to intractable right flank pain. MRI demonstrated an eight cm, heterogeneous, septate, right adrenal mass suspected to be either pheochromocytoma/paraganglioma (PPGL), adrenocortical carcinoma or metastasis. Blood metanephrines were sent urgently to enable a safe delivery and were within normal range, as were cortisol and androgen levels. A biopsy was taken from a palpable breast mass as well as from an ovarian mass during the operation. At 36 weeks gestation, she was delivered by cesarean section. PET computed tomography performed after delivery revealed the extensive metastatic spread of recurring melanoma including the right adrenal gland. Timely diagnosis and management by a multidisciplinary team are important to avoid a catastrophic outcome. There is no consensus on optimal management and timing of delivery. PPGL should be ruled out before delivery.

To assess whether pre-labor measurement of the angle of progression (AOP) can assist in predicting a successful vaginal birth after cesarean in women without a previous vaginal birth.A prospective observational cohort study performed in a single tertiary center including women at term with a single previous cesarean delivery (CD), without prior vaginal births, who desire a trial of labor. Transperineal ultrasound was used to measure the AOP before the onset of labor. The managing staff in the delivery suite was blinded to the ultrasound measurements. Clinical data and delivery outcome were retrieved from medical records. The study was approved by the institutional ethics committee (KMC 0117-10).Of the 111 women included in the study, 67 (60.4%) had a successful vaginal birth after CD. Women were sonographically assessed at a median of 3 days [interquartile range (IQR) 1-3 days] prior to delivery. The median AOP was significantly narrower in women who eventually underwent a CD than in those who delivered vaginally (88°, IQR 78-96° vs. 99°, IQR 89-107°, respectively;Pre-labor AOP may be a useful sonographic tool for predicting vaginal birth after CD and can assist in consulting primiparous women with a prior CD opting for a trial of labor.

To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations.This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count.Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.

Post-bariatric surgery hypoglycemia (PBH) is a serious and relatively prevalent complication of bariatric surgery and is often underdiagnosed due to unawareness. PBH can have a profound effect on health and quality of life. Data regarding the natural history and management of PBH during pregnancy are lacking. Here we describe a case of a 34-year-old woman who presented with intractable PBH during the second trimester of her third pregnancy, three years after a Roux-en-Y gastric bypass (RYGB). Treatment with nifedipine showed partial response and eventually intravenous (IV) glucose was needed until birth.

Background: The optimal treatment strategy for the follow-up and management of women with glucokinase maturity-onset diabetes of the young (GCK−MODY)during pregnancy remains unknown. Data regarding maternal and fetal outcomes are lacking. Aim: This paper summarizes the existing literature regarding the maternal and fetal outcomes of women with glucokinase MODY to guide future treatment strategy. Methods: A literature search was conducted in Pubmed, Embace, and Cochrane library with citation follow-up using the terms: glucokinase, MODY, diabetes, pregnancy, gestation, and outcomes. We searched for articles with known fetal mutational status. Relevant outcomes included: birthweight, large for gestational age (LGA), small for gestational age (SGA), macrosomia, cesarean delivery (CD), shoulder dystocia, congenital anomalies, miscarriages, preterm births, and long-term outcomes. Results: Fourteen relevant manuscripts were identified describing maternal and fetal outcomes. The percentage of LGA and macrosomia in 102 glucokinase -unaffected offspring (GCK−) was significantly higher than in the glucokinase -affected offspring (GCK+) (44% vs. 10%, p < 0.001 and 22% vs. 2%, p < 0.001, respectively). Among the 173 GCK(+) offspring, only 5% were SGA, which can be expected according to the normal distribution. We observed higher rates of CD and shoulder dystocia in the GCK(−) offspring. Conclusions: GCK(−) offspring have significantly higher birthweights and more birth complications. The optimal treatment strategy to guide management should take into consideration multiple variables other than fetal mutational status.

Aims Assessing the value of oral glucose tolerance test performed at term pregnancy in identifying obstetric complications. Methods Retrospective cohort study of women with a normal 50 g glucose challenge test who also had an oral glucose tolerance test at term (defined as at or after 37 weeks of gestation). Comparison between the pathological and normal oral glucose tolerance test groups was performed. Results The mean glucose in the glucose challenge test of women in the normal oral glucose tolerance test ( n = 256) group was lower than that in the pathological oral glucose tolerance test ( N = 16) group (105 ± 17 mg/dl (5.8 ± 0.9 mmol/l) vs 117 ± 13 mg/dl (6.5 ± 0.7 mmol/l), p = 0.007). Relevant obstetrical complications did not differ significantly between the groups. Of note, in the pathological oral glucose tolerance test group only one woman delivered a macrosomic infant. Conclusions A pathological oral glucose tolerance test performed at term was unable to identify women at risk for impaired glucose metabolism-related obstetric complications and is therefore of limited clinical value and seems to be unjustified.

OBJECTIVE: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus. METHODS: This cross-sectional study included women in the following groups: 1) normal pregnancy (NP) (n=49); 2) PE (n=56); and 3) SGA (n=28). Maternal plasma thrombin generation (TGA) was measured, calculating: a) lag time (LT); b) velocity index (VI); c) peak thrombin concentration (PTC); d) time-to-peak thrombin concentration (TPTC); and e) endogenous thrombin potential (ETP). RESULTS: 1) The median TPTC, VI, and ETP differed among the groups (p=0.001, p=0.006, p

Objectives To assess whether measurement of the angle of progression (AOP) before induction of labor (IOL) can predict successful vaginal delivery in nulliparous women. Methods This was a prospective, observational study of nulliparous women with a singleton term pregnancy and an indication for IOL. Transperineal sonography was used to measure the AOP before cervical ripening. Since all women enrolled had a low Bishop score, 98.6% of them were induced with either intracervical extra-amniotic balloon catheter or vaginal prostaglandin E-2. The staff in the labor ward were blinded to the AOP measurements. Clinical data were retrieved from computerized medical records. Results Of the 150 women included in the final analysis, 40 (26.7%) delivered by Cesarean section. The median AOP was narrower in women who had a Cesarean delivery than in those who delivered vaginally (90° (interquartile range (IQR), 84-94.5°) vs 98° (IQR, 90.8-105°); P 92° (derived from a receiver-operating characteristics curve) was associated with a successful vaginal delivery in 94.8% of women. Multivariate stepwise logistic regression analysis including maternal age, body mass index, gestational age, estimated fetal weight, fetal head station, indication for IOL and AOP demonstrated that only AOP was independently associated with the prediction of a successful induction. Conclusion AOP may be a useful sonographic parameter for predicting successful vaginal delivery among nulliparous women at term undergoing IOL; an AOP wider than 92° is associated with a high rate of vaginal delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Longer duration of active pushing during labor is associated with a higher rate of operative delivery and an increased risk of maternal and neonatal complications. Although immediate pushing at complete dilatation is associated with lower rates of chorioamnionitis and postpartum hemorrhage, it is also associated with a longer duration of pushing.This study aimed to evaluate whether fetal head station and position, as assessed by ultrasound at the beginning of the pushing process, can predict the mode of delivery and duration of pushing in nulliparous women.This prospective observational study included nulliparous women with neuraxial analgesia and complete cervical dilatation. The following sonographic parameters were assessed just before the beginning of the pushing process, at rest, and while pushing during contraction: head position, angle of progression, head-perineum distance, and head-symphysis distance. The change between rest and pushing was designated as delta angle of progression, delta head-perineum distance, and delta head-symphysis distance. The sonographic measurements and fetal head station assessed by vaginal examination were compared between women who had a spontaneous vaginal delivery to those who underwent an operative delivery, and between those who pushed for more or less than 1 hour.Of the 197 women included in this study, 166 (84.3%) had a spontaneous vaginal delivery, 31 (15.7%) had an operative delivery, 23 (11.6%) had a vacuum delivery, and 8 (4.0%) had a cesarean delivery. Spontaneous vaginal delivery and shorter duration of pushing (less than an hour) were significantly more common with a nonocciput posterior position (10.6% vs 47.3%; P.005), a wider angle of progression, a shorter head-perineum distance and head-symphysis distance (both during rest and while pushing), and a lower fetal head station as assessed by digital vaginal examination. However, a logistic regression model revealed that only the angle of progression at rest and the delta angle of progression were independently associated with a spontaneous vaginal delivery with an area under the curve of 0.82 (95% confidence interval, 0.76-0.87; P.0001) and 0.75 (95% confidence interval, 0.67-0.79; P.0001), respectively.Ultrasound performed at the beginning of the active second stage of labor can assist in predicting the mode of delivery and duration of pushing and perform better than the traditional digital examination, with the angle of progression at rest and delta angle of progression being the best predictors.

Objective This study sought to compare the value of transvaginal ultrasonography (TVUS) and hysteroscopy in premenopausal and postmenopausal women in the diagnosis of endometrial polyp. Methods The records of 694 women with an ultrasonographic diagnosis of suspected endometrial polyp who underwent hysteroscopy were studied. Patients were divided into two groups according to menopausal status, and a comparison was made between two groups. Results There were 299 postmenopausal and 395 premenopausal women in the study. Hysteroscopy confirmed the ultrasonographic diagnosis of endometrial polyp in 212 (71%) and 212 (53%) patients in the postmenopausal and premenopausal groups, respectively (P = 0.001). In postmenopausal patients, 94% of the polyps observed by hysteroscopy were confirmed by histology, whereas in premenopausal patients, the percentage was 85% (P = 0.004). Conclusion In premenopausal patients, the diagnostic value of TVUS and hysteroscopy is lower than in postmenopausal patients. The appropriate time for TVUS and hysteroscopy should be scheduled in premenopausal women, especially in women with abnormal uterine bleeding.

Objective The reported frequency of malignant or premalignant changes confined to endometrial polyps (EP) is 0.5–6%. The management of atypical endometrial hyperplasia (AEH) confined to EP is not yet established. Recently, an alternative pathological nomenclature has emerged using the term endometrial intraepithelial neoplasia (EIN) instead of atypia. The objective of this study was to evaluate the safety of conservative hysteroscopic resection of endometrial polyps with AEH or EIN. Methods Retrospective cohort study of all cases of hysteroscopic resections of EP was performed at a single center between the years 2000–2011. All patients with a pathologic diagnosis of AEH in EP were included. A post-hoc revision of the pathologic specimens was made according to the EIN classification. Results Of the 32 patients with AEH in EP, 25 had normal endometrial curetting. Even with AEH confined to EP, 12 cases (48%) showed AEH (11 cases) or carcinoma (1 case) in the hysterectomy specimens. EIN in EP (14 cases) was correlated with 57% of diagnosis of EIN or carcinoma in the uterus; whereas in the absence of EIN in EP only 1 of 9 cases showed EIN in the final pathologic specimen (p=0.002), and none with carcinoma, which yields a PPV of 14% and a NPV of 100%. Conclusion The diagnosis of EIN in EP may be a better predictor than AEH for endometrial involvement with malignant or pre-malignant neoplasms. The safety of conservative hysteroscopic resection of EP with AEH/EIN is questioned.

OBJECTIVE: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and a small-for-gestational-age (SGA) neonate differs from that of women with normal pregnancy and whether they are related to specific placental lesions.. METHODS: This cross-sectional study included the following groups: 1) normal pregnancy (n=68); 2) PE (n= 128); and 3) SGA (n=56). Maternal plasma TF and TFPI activity was determined with chromogenic assays. RESULTS: 1) The median maternal plasma TF activity, but not TFPI activity, differed among the study groups (p

Objective:The aim of this study was to determine gene expression and splicing changes associated with parturition and regions (visceral vs. subcutaneous) of the adipose tissue of pregnant women.Study design:The transcriptome of visceral and abdominal subcutaneous adipose tissue from pregnant women at term with (n=15) and without (n=25) spontaneous labor was profiled with the Affymetrix GeneChip Human Exon 1.0 ST array. Overall gene expression changes and the differential exon usage rate were compared between patient groups (unpaired analyses) and adipose tissue regions (paired analyses). Selected genes were tested by quantitative reverse transcription-polymerase chain reaction.Results:Four hundred and eighty-two genes were differentially expressed between visceral and subcutaneous fat of pregnant women with spontaneous labor at term (q-value 1.5). Biological processes enriched in this comparison included tissue and vasculature development as well as inflammatory and metabolic pathways. Differential splicing was found for 42 genes [q-value 2] between adipose tissue regions of women not in labor. Differential exon usage associated with parturition was found for three genes (Conclusion:We show for the first time evidence of implication of mRNA splicing and processing machinery in the subcutaneous adipose tissue of women in labor compared to those without labor.

Background/Aims: The study aimed to assess whether the use of intrapartum transperineal ultrasound (US) can reduce the rate of failed vacuum extraction (VE). Methods: This is a retrospective cohort study including all women delivering at term with the diagnosis of protracted second stage of labor. The mode of delivery and rate of failed VE were compared between women who underwent a US examination prior to the decision on obstetrical interventions (“+US” group) and those in whom clinical decisions were based upon digital assessment only (“no-US” group). Results: The study included 635 women. Among the “no-US” group (536), there were 13 failed VE attempts (3.6%) vs. none in the “+US” group (99, p = 0.1). There was a significant difference between the groups regarding mode of delivery (p = 0.001), with a lower cesarean section (CS) rate (20.2 vs. 27.8%) among the “+US” group. Maternal age, body mass index, nulliparity, gestational age at delivery, and birth weight, as well as neonatal short-term outcome did not differ significantly between the 2 groups. Conclusions: We demonstrate that among women who had the addition of intrapartum US during the second stage of labor there was a trend toward a lower rate of failed VE (although not reaching statistical significance), with a lower rate of CS but not affecting neonatal outcome.

Objectives The angle of progression (AOP), measured by transperineal ultrasound, has been used to assess fetal head descent during labor. Our aim was to assess whether, before onset of labor, parous women have a narrower AOP than do nulliparous women and if a narrow AOP is associated with a higher rate of Cesarean delivery. Methods In this prospective, observational study, we performed transperineal ultrasound in pregnant women not yet in labor at ≥ 39 weeks' gestation who delivered within 1 week of sonography. The AOP was compared as follows: in nulliparous women, between those who had a Cesarean section and those who delivered vaginally; and among women who delivered vaginally, between those who were nulliparous and those who were parous. Results Included in the study were 100 nulliparous and 71 parous women. Among those who delivered vaginally (n = 161), the median AOP before onset of labor was narrower in parous than in nulliparous women (98° (interquartile range (IQR)), 90–107° vs 104° (IQR, 97–113°), P < 0.001). Among the 100 nulliparous women, (1) the median AOP before onset of labor was narrower in those who went on to deliver by Cesarean section (n = 9) than in those delivered vaginally (n = 91) (90° (IQR, 85.5–93.5°) vs 104° (IQR, 97–113°), P < 0.001); (2) an AOP ≥ 95° (derived from the receiver–operating characteristics curve) was associated with vaginal delivery in 99% of women; and (3) 89% (8/9) of women who delivered by Cesarean section had an AOP < 95°. Among the 71 parous women, only one delivered by Cesarean section and all of those with an AOP < 95° delivered vaginally. Conclusion A narrow AOP (< 95°) in non-laboring nulliparous women at term is associated with a high rate of Cesarean delivery. Parous women have a narrower AOP than do nulliparous women before the onset of labor; however, unlike in nulliparous women, a narrow AOP in parous women does not appear to be associated with Cesarean delivery and most parous women with such an angle go on to deliver vaginally. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Congenital varicella syndrome, maternal varicella-zoster virus pneumonia and neonatal varicella infection are associated with serious fetomaternal morbidity and, not infrequently, mortality. Vaccination against varicella-zoster virus can prevent the disease, and outbreak control limits the exposure of pregnant women to the infectious agent. Maternal varicella-zoster immunoglobulin administration before rash development, with or without antiviral medication, can modify the progression of the disease.

Objective To describe a novel and simple algorithm (four-chamber view and ‘swing technique’ (FAST) echo) for visualization of standard diagnostic planes of fetal echocardiography from dataset volumes obtained with spatiotemporal image correlation (STIC) and applying a new display technology (OmniView). Methods We developed an algorithm to image standard fetal echocardiographic planes by drawing four dissecting lines through the longitudinal view of the ductal arch contained in a STIC volume dataset. Three of the lines are locked to provide simultaneous visualization of targeted planes, and the fourth line (unlocked) ‘swings’ through the ductal arch image (swing technique), providing an infinite number of cardiac planes in sequence. Each line generates the following plane(s): (a) Line 1: three-vessels and trachea view; (b) Line 2: five-chamber view and long-axis view of the aorta (obtained by rotation of the five-chamber view on the y-axis); (c) Line 3: four-chamber view; and (d) ‘swing line’: three-vessels and trachea view, five-chamber view and/or long-axis view of the aorta, four-chamber view and stomach. The algorithm was then tested in 50 normal hearts in fetuses at 15.3-40 weeks' gestation and visualization rates for cardiac diagnostic planes were calculated. To determine whether the algorithm could identify planes that departed from the normal images, we tested the algorithm in five cases with proven congenital heart defects. Results In normal cases, the FAST echo algorithm (three locked lines and rotation of the five-chamber view on the y-axis) was able to generate the intended planes (longitudinal view of the ductal arch, pulmonary artery, three-vessels and trachea view, five-chamber view, long-axis view of the aorta, four-chamber view) individually in 100% of cases (except for the three-vessels and trachea view, which was seen in 98% (49/50)) and simultaneously in 98% (49/50). The swing technique was able to generate the three-vessels and trachea view, five-chamber view and/or long-axis view of the aorta, four-chamber view and stomach in 100% of normal cases. In the abnormal cases, the FAST echo algorithm demonstrated the cardiac defects and displayed views that deviated from what was expected from the examination of normal hearts. The swing technique was useful for demonstrating the specific diagnosis due to visualization of an infinite number of cardiac planes in sequence. Conclusions This novel and simple algorithm can be used to visualize standard fetal echocardiographic planes in normal fetal hearts. The FAST echo algorithm may simplify examination of the fetal heart and could reduce operator dependency. Using this algorithm, inability to obtain expected views or the appearance of abnormal views in the generated planes should raise the index of suspicion for congenital heart disease. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Caesarean delivery is frequently complicated by surgical site infections, endometritis and urinary tract infection. Most surgical site infections occur after discharge from the hospital, and are increasingly being used as performance indicators. Worldwide, the rate of caesarean delivery is increasing. Evidence-based guidelines recommended the use of prophylactic antibiotics before surgical incision. An exception is made for caesarean delivery, where narrow-range antibiotics are administered after umbilical cord clamping because of putative neonatal benefit. However, recent evidence supports the use of pre-incision, broad-spectrum antibiotics, which result in a lower rate of maternal morbidity with no disadvantage to the neonate.

Human parvovirus B19 infection is widespread. Approximately 30-50% of pregnant women are nonimmune, and vertical transmission is common following maternal infection in pregnancy. Fetal infection may be associated with a normal outcome, but fetal death may also occur without ultrasound evidence of infectious sequelae. B19 infection should be considered in any case of nonimmune hydrops. Diagnosis is mainly through serology and polymerase chain reaction. Surveillance requires sequential ultrasound and Doppler screening for signs of fetal anaemia, heart failure and hydrops. Immunoglobulins, antiviral and vaccination are not yet available, but intrauterine transfusion in selected cases can be life saving.

The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia.Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis.(1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6.An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.

The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine–cytokine receptor interaction with downregulation of IL-1β, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.

Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women.This cross-sectional study included patients with a normal pregnancy (n = 33), preeclampsia (n = 33), and an SGA without preeclampsia (n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value0.01 was considered statistically significant.(1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy (p0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes (p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate (p = 0.003 and p = 0.002, respectively).Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia.

Problem Resistin, originally described as an adipokine, has emerged as a potent pro-inflammatory protein associated with both acute and chronic inflammation. Moreover, resistin has been proposed as a powerful marker of sepsis severity, as well as a predictor of survival of critically ill non-pregnant patients. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma resistin concentrations.

Citation Vaisbuch E, Romero R, Erez O, Mazaki-Tovi S, Kusanovic JP, Soto E, Dong Z, Chaiworapongsa T, Kim SK, Ogge G, Pacora P, Yeo L, Hassan SS. Activation of the alternative pathway of complement is a feature of pre-term parturition but not of spontaneous labor at term. Am J Reprod Immunol 2010; 63: 318–330 Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery

The importance of an anti-angiogenic state as a mechanism of disease in preeclampsia is now recognized. Assays for the determination of concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF) and soluble endoglin (sEng) have been developed for research and clinical laboratories. A key question is whether these factors should be measured in plasma or serum. The purpose of this study was to determine if there are differences in the concentrations of these analytes between plasma and serum in normal pregnancy and in preeclampsia.Samples of maternal blood were obtained by venipuncture and collected in EDTA (lavender top) and serum collection tubes (red top). A standard laboratory procedure was implemented for the centrifugation, aliquoting and storage of samples. Plasma and serum from 70 women with normal pregnancies and 34 patients with preeclampsia were assayed for sVEGFR-1, sVEGFR-2, PlGF and sEng by ELISA. Nonparametric paired tests were used for analyses.A significant difference between plasma and serum concentration was observed for sVEGFR-1 and sVEGFR-2 in normal pregnancy, and for sVEGFR-1, sVEGFR-2, PlGF and sEng in women with preeclampsia.The concentrations of sVEGFR-1, sVEGFR-2, PlGF and sEng when measured in maternal plasma and in serum are different. Therefore, the matrix used for the assay (serum versus plasma) needs to be considered when selecting thresholds for predictive studies and interpreting the growing body of literature on this subject.

Citation Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Nhan-Chang C-L, Gomez R, Yoon BH, Yeo L, Mittal P, Ogge G, Gonzalez JM, Hassan SS. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol 2010; 63: 252–262 Problem Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients. Method of study This cross-sectional study included the following groups: (1) normal pregnant women (n = 200) and (2) pregnant women with pyelonephritis (n = 40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. Results (1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; (2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and (3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational body mass index, smoking status, gestational age at sampling, and birthweight. Conclusion Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy.

Angiogenic factors have been implicated in the pathophysiology of sepsis. In experimental models of sepsis (endotoxemia and/or cecal ligation puncture), there is increased expression of vascular endothelial growth factors (VEGF) and the administration of exogenous soluble VEGF receptor (sVEGFR)-1, an antagonist to VEGF, reduces morbidity and mortality. Moreover, a dramatic elevation in sVEGFR-1 has been demonstrated in human sepsis. Although a balance between angiogenic and anti-angiogenic factors is essential for feto-placental development, the changes of angiogenic factors during pregnancy in the context of infection have never been explored. Angiogenic factors also play crucial roles in the pathophysiology of preeclampsia (PE). This study was conducted to determine if maternal plasma concentrations of placental growth factor (PlGF), sVEGFR-2, and soluble endoglin (sEng) change in pregnancies complicated by acute pyelonephritis (AP) compared with normal pregnancy and PE.A case-control study was conducted in patients with AP, normal pregnant (NP) women, and patients with PE (n=36 for each group) matched for gestational age. AP was diagnosed in the presence of fever (temperatureor=38 degrees C), clinical signs of infection, and a positive urine culture for microorganisms. Plasma concentrations of PlGF, sVEGFR-2, and sEng were determined by ELISA. The results of plasma sVEGFR-1 concentrations have previously been reported, but were included in this study to provide a complete picture of the angiogenic/anti-angiogenic profiles. Serum concentrations of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-gamma, granulocyte macrophage colony stimulating factor, and tumor necrosis factor (TNF) were also determined using high sensitivity multiplexed immunoassays in patients with AP and NP.AP was associated with a lower median plasma concentration of PlGF and sVEGFR-2 than NP (both p0.001). There were no significant differences in the median plasma concentrations of sEng and sVEGFR-1 between AP and NP (p=0.7 and 0.5, respectively). In contrast, there was a 5-fold decrease of the median plasma concentration of PlGF, and an 8-10-fold increase of the median plasma concentrations of sVEGFR-1 and sEng in PE compared with those in AP (all p0.001). No significant difference in the median plasma concentration of sVEGFR-2 was observed between patients with PE and AP (p=0.5). Pregnant women with AP had median plasma concentrations of IL-6, IL-7, IL-8, IL-10, IFN-gamma, and TNF-alpha significantly higher than those in NP women (all p0.001, except IL-7 p=0.004).AP is associated with changes in the profile of angiogenic and anti-angiogenic factors. Although some of these changes resemble those in PE (decreased PlGF and sVEGFR-2), the magnitude of the changes of PlGF is much higher in PE. We conclude that despite high plasma inflammatory cytokine concentrations, acute systemic inflammation in pregnancy has a different angiogenic/anti-angiogenic profile than that of PE.

Objective. Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI).Study design. This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI. sHLA-G concentrations were determined by EL...

Increased amniotic fluid concentrations of anti-microbial peptides, components of the innate immune system, have been reported in patients with preterm labor (PTL) with intact membranes and intra-amniotic infection and/or inflammation (IAI), as well as in patients with preterm prelabor rupture of the membranes (PPROM). This study was designed to confirm these results using a targeted approach, detecting DEFA1, DEFB1, GNLY, and S100A9 gene expression in the choriamniotic membranes in pregnancies complicated with PTL and intact membranes or PPROM, with and without histologic chorioamnionitis.Human fetal membranes were obtained from patients in the following groups: (1) PTL with intact membranes (n = 15); (2) PTL with intact membranes with histologic chorioamnionitis (n = 12); (3) PPROM (n = 17); and (4) PPROM with histologic chorioamnionitis (n = 21). The mRNA expression of alpha-defensin-1, beta-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR.(1) The expression of alpha-defensin-1 mRNA in the fetal membranes was higher in patients with PTL and intact membranes with histologic chorioamnionitis, than those without chorioamnionitis (19.4-fold, p0.001); (2) Among patients with histologic chorioamnionitis, patients with PTL and intact membranes had a higher alpha-defensin-1 mRNA expression than those with PPROM (5.5-fold, p = 0.003); (3) Histologic chorioamnionitis was associated with a higher calgranulin B mRNA expression in the chorioamniotic membranes of patients with both PTL and intact membranes (7.9-fold, p = 0.03) and PPROM (7.6-fold, p0.0001); (4) The expression of calgranulin B mRNA in the fetal membranes was higher in patients with PTL and intact membranes without histologic chorioamnionitis than in those with PPROM without histologic chorioamnionitis (2.7-fold, p = 0.03); (5) There were no differences in the expression of beta-defensin-1 and granulysin in the chorioamniotic membranes between the study groups even in the presence of histologic chorioamnioniotis.(1) Among patients with histologic chorioamnionitis, the mRNA expression of alpha-defensin-1 and calgranulin B in the fetal membranes of patients with PTL and intact membranes as well as that of calgranulin B in the fetal membranes of patients with PPROM is higher than in the membranes of those without histologic chorioamnionitis; (2) histologic chorioamnionitis is associated with differences in the pattern of alpha-defensin-1 mRNA expression in the fetal membranes in patients with PTL and intact membranes and those with PPROM.

Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia.This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6-15 weeks) and midtrimester (20-25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of0.05 was considered significant.(1) The prevalence of preeclampsia, term, preterm, (37 weeks) and early-onset preeclampsia (34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98-99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia.(1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGF/sEng.

OBJECTIVE The objective of this study was to quantify the repeatability and reproducibility of fetal cardiac ventricular volumes obtained using spatiotemporal image correlation (STIC) and Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria). METHODS A technique was developed to compute ventricular volumes using the subfeature Contour Finder: Trace. Twenty-five normal pregnancies were evaluated for the following: (1) to compare the coefficient of variation (CV) of ventricular volumes obtained using 15 degrees and 30 degrees rotation; (2) to compare the CV between 3 methods of quantifying ventricular volumes: (a) Manual Trace, (b) Inversion Mode, and (c) Contour Finder: Trace; and (3) to determine repeatability by calculating agreement and reliability of ventricular volumes when each STIC was measured twice by 3 observers. Reproducibility was assessed by obtaining 2 STICs from each of 44 normal pregnancies. For each STIC, 2 ventricular volume calculations were performed, and agreement and reliability were evaluated. Additionally, measurement error was examined. RESULTS (1) Agreement was better with 15 degrees rotation than 30 degrees (15 degrees: 3.6%; 95% confidence interval [CI], 3.0%-4.2%; versus 30 degrees: 7.1%; 95% CI, 5.8%-8.6%; P < .001); (2) ventricular volumes obtained with Contour Finder: Trace had better agreement than those obtained using either Inversion Mode (Contour Finder: Trace: 3.6%; 95% CI, 3.0%-4.2%; versus Inversion Mode: 6.0%; 95% CI, 4.9%-7.2%; P < .001) or Manual Trace (10.5%; 95% CI, 8.7%-12.5%; P < .001); (3) ventricular volumes were repeatable with good agreement and excellent reliability for both intraobserver and interobserver measurements; and (4) ventricular volumes were reproducible with negligible differences in agreement and good reliability. In addition, bias between STIC acquisitions was minimal (

Objective: Several mechanisms of disease have been implicated in the pathophysiology of small-for-gestational-age (SGA) including an anti-angiogenic state, and an exaggerated intravascular pro-inflammatory response. Adiponectin plays a role in a wide range of biological activities including those that have been implicated in the pathophysiology SGA. Thus, the aim of this study was to determine if third trimester adiponectin concentrations differed between women with normal weight infants and those with an SGA neonate. Study design: This cross-sectional study included women with: 1) a normal pregnancy (n=234); and 2) an SGA neonate (n=78). SGA was defined as a birth weight below the 10th percentile for gestational age at birth. The study population was further stratified by first trimester body mass index (BMI) (normal weight 2 vs. overweight/obese ≥25 kg/m2). Maternal serum adiponectin multimers [total, high-molecular-weight (HMW), medium-molecular-weight (MMW) and low-molecular-weight (LMW)] concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median maternal serum concentrations of total, HMW and MMW adiponectin were significantly lower in patients with an SGA neonate than in those with normal pregnancies; 2) patients with an SGA neonate had a significantly lower median HMW/total adiponectin ratio and higher median MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy; 3) among patients with an SGA neonate, neither maternal serum concentrations of adiponectin multimers, nor their relative distribution differ between normal weight and overweight/obese patients. Conclusion: 1) Pregnancies complicated by an SGA neonate are characterized by a alterations in the maternal serum adiponectin multimers concentrations and their relative abundance; 2) the findings reported herein suggest that maternal adipose tissue may play a role, in the pathogenesis of SGA.

Objective: Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design: This cross-sectional study included 486 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=48) and without (n=45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n=152); b) PTL without IAI who delivered preterm ( Results: 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P Conclusions: 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation.