Inflammasome activation in preeclampsia and intrauterine growth restriction.

PROBLEM: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8%-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR. METHODS OF STUDY: In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. RESULTS: NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples versus NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. CONCLUSIONS: NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR.

Inflammasome activation in preeclampsia and intrauterine growth restriction.

PROBLEM: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR. METHODS OF STUDY: In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. RESULTS: NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples vs. NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. CONCLUSIONS: NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR. This article is protected by copyright. All rights reserved.

Elevated expression of galectin-3, thioredoxin and thioredoxin interacting protein in preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a pregnancy-related syndrome characterized by the onset of hypertension and proteinuria that can lead to end-organ dysfunction. Galectin-3 (Gal-3) is involved in cell growth, differentiation, inflammation and fibrosis. Thioredoxin (TXN) acts as antioxidant enzyme in several cellular processes, regulating inflammation and inhibiting apoptosis. TXNIP is an endogenous inhibitor of TXN. We evaluated changes in the inflammatory response of Gal-3, TXN, and TXNIP at the level of maternal blood, placenta, and umbilical cord blood of women with PE. STUDY DESIGN: Ten women with PE and 20 with normal pregnancy (NP) were recruited during admission for delivery. Blood samples were obtained from parturients and umbilical cords, and placental tissue for analysis. RESULTS: Gal-3 and TXNIP mRNA expression were higher in maternal plasma in PE group compared to NP and were lower in cord blood plasma and placentas in the PE group. In the PE group, TXN/TXNIP mRNA ratio was higher in cord blood plasma (2.07) compared to maternal plasma (1.09). TXN/TXNIP placental protein ratio was similar between PE (0.89) and NP (0.79). ELISA demonstrated that Gal-3 levels in maternal serum were significantly higher in the PE vs. the NP group. CONCLUSIONS: Pro-inflammatory changes were expressed by high Gal-3 and TXNIP mRNA in maternal blood of PE women, but not in their placental and cord blood samples. These findings may imply that the placenta has a role in protecting the fetus from the damages of inflammatory response, which is more common in PE than in NP.

Enhanced expression of Galectin-3 in gestational diabetes.

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications. METHODS AND RESULTS: Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar. CONCLUSION: Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet.

Postpartum visits in the gynecological emergency room: How can we improve?

BACKGROUND: The attendance to the gynecological-emergency-room (GER) of women only a few weeks following previous discharge after birth comprises a medical as well as social problem. The objective of the study was to characterize the postpartum women that attended the GER, and depict the leading etiologies and risk-factors that lead them to attend the GER, and to examine correlations between their medical findings at discharge and the reasons for their attendance to the hospital. METHODS: All women that attended the GER between 01/01/2016 and 30/09/2016 during 6 weeks after birth were included. The variables assessed were: medical history, mode of birth, maternal complications of birth, diagnosis at the GER, treatment received and readmission. RESULTS: There were 446 visits of 413 women (5.6% of all deliveries). Most were generally healthy after their first normal vaginal birth with no complications during or following birth. 38.7% had a cesarean birth (p < 0.001). The most common causes of the visits were fever (30.3%), problems in episiotomy or surgical scar (26.6%) and abdominal pain (25.7%). Women with hypertensive disorders during birth had significantly more hypertensive problems in the GER. Diabetic women suffered statistically more from hypertensive disorder in the GER. 33.2% were examined and found healthy. Seventy-two women (1% of all deliveries) were hospitalized, most of them due to infection. Only 7.5% were referred to the GER due to bleeding. CONCLUSIONS: Postpartum women are at risk of morbidities, especially following cesarean sections and in women with hypertensive disorders of during pregnancy. Scheduled visits to high-risk women to attend outpatient clinic sooner are recommended.

The temporal effect of Category II fetal monitoring on neonatal outcomes.

OBJECTIVE: To correlate the duration of Category II cardiotocograms (CTG) with adverse neonatal outcomes associated with perinatal asphyxia and determine the duration before fetal compromise. STUDY DESIGN: This retrospective, observational study used electronic medical record data from a cohort of 271 patients, delivered by C-section due to non-reassuring fetal heart rate, at a tertiary medical center, from 2015 through 2017. Duration of Category II CTG, variability, tachycardia and deceleration frequency were analyzed and correlated to immediate postnatal outcomes. including cord pH ≤ 7, cord base excess >12, 1- and 5-min Apgar scores ≤7, need for ventilation, need for chest compressions, NICU admission, hypoglycemia and convulsions. Intrapartum fever and meconium stained amniotic fluid were correlated to the same outcomes. Categorical and continuous variables were analyzed using chi-square and t-tests, respectively. P < 0.05 was considered significant. RESULTS: The mean duration of Category II CTG was 146 min (range 17-553). Longer duration did not result in increased rates of adverse neonatal outcomes. In contrast, reduced fetal heart rate (FHR) variability, fetal tachycardia and intrapartum fever did show increased rates of adverse neonatal outcomes, as follows: patients exhibiting reduced vs. normal (FHR) variability had 12.9% vs. 1.4% cord pH ≤ 7, P = 0.006 and 12.5% vs. 1.3% cord BE > 12, P = 0.004: patients with fetal tachycardia vs. normal baseline FHR exhibited 48% vs. 17.9% 1-minute Apgar score ≤7, P = 0.0004; 8% vs. 0.8% 5-minute Apgar score ≤7, P = 0.04; and 48% vs. 18.7% ventilation support, P < 0.001; patients with intrapartum fever vs. normal temperature, cord BE > 12 was seen in 9.7% vs. 1.7%, P = 0.035; 1-minute Apgar score was ≤7 in 35.5% vs. 18.7%, P = 0.03; 5-minute Apgar score ≤7 in 9.7% vs. 0.4%, P = 0.005; need for ventilation in 35.5% vs. 19.6%, P = 0.042; need for chest compressions in 6.45% vs. none, P = 0.013; and NICU admission in 12.9% vs. 2.5%, P = 0.018. CONCLUSIONS: Our results suggest that the duration of Category II CTG alone does not appear to predict perinatal asphyxia. Parameters associated with perinatal asphyxia are reduced FHR variability, fetal tachycardia and intrapartum fever. Therefore, when contemplating intervention during labor to avoid fetal asphyxia, these parameters should be strongly considered.

Differentiating the QRS Morphology of Posterior Fascicular Ventricular Tachycardia From Right Bundle Branch Block and Left Anterior Hemiblock Aberrancy.

BACKGROUND: Left posterior fascicular ventricular tachycardia (LPF-VT) is frequently misdiagnosed as supraventricular tachycardia with aberrant right bundle branch block (RBBB) and left anterior hemiblock (LAHB). The purpose of the present study was to define the morphological ECG characteristics of LPF-VT and attempt to differentiate it from RBBB and LAHB aberrancy. METHODS AND RESULTS: A systematic Medline search was used to identify or locate ECG tracings from patients with LPF-VTs. ECGs with LPF-VT were also collected from patients who underwent ablation of this arrhythmia at the Tel Aviv and Sheba Medical Centers. These ECGs were compared with ECGs of consecutive patients with RBBB and LAHB and no obvious cardiac pathology by echocardiography. Overall, 183 ECGs of LPF-VT were compared with 61 ECGs showing RBBB and LAHB. Univariate analysis demonstrated differences in QRS axis, limb (I, aVr), and precordial (V1, V2, V6) ECG leads. On multivariate logistic regression analysis, LPF-VT was more often associated with atypical RBBB-like V1 morphology (odds ratio, 5.1; P=0.004), positive QRS in aVr (odds ratio, 19.2; P<0.001), V6 R/S ratio ≤1 (odds ratio, 6.7; P=0.01), and QRS ≤140 ms (odds ratio, 7.7; P<0.001). Using these 4 variables, a prediction model was developed that predicted LPF-VT with sensitivity and specificity of 82.1% and 78.3%, respectively. Patients with 3 of 4 positive variables had high probability of having LPF-VT, whereas patients with ≤1 positive variable always had RBBB plus LAHB. CONCLUSIONS: The morphological ECG characteristics of LPF-VT were defined, and a high accurate tool for correctly differentiating LPF-VT from RBBB and LAHB aberrancy was developed.