Evidence from human placenta, ER-stressed trophoblasts and transgenic mice links transthyretin proteinopathy to preeclampsia

We have demonstrated that protein aggregation plays a pivotal role in the pathophysiology of preeclampsia (PE) and identified several aggregated proteins in the circulation of PE patients, most significantly the serum protein transthyretin (TTR). Here we show robust accumulation of TTR aggregates in the placentas of women with early-onset PE (e-PE). TTR aggregation was inducible in primary human trophoblasts (PHTs) and the TCL-1 trophoblast cell line by ER stress inducers or autophagy-lysosomal disruptors. Hypoxia/reoxygenation (H/R) of cultured PHTs increased intracellular BiP, phosphorylated IRE1alpha, PDI and Ero-1, all markers of the UPR, and the apoptosis mediator caspase-3. Blockade of IRE1alpha inhibited H/R-induced upregulation of Ero-1 in PHTs. Excessive UPR was observed in the PE placenta. Further, pregnant mice, overexpressing transgene encoded wild type human TTR, displayed aggregated TTR in the junctional zone of the placenta and PE-like features including hypertension, proteinuria, intrauterine growth restriction, kidney injury, and elevated levels of the PE biomarkers serum sFlt-1 and endoglin. High Resolution Ultrasound analysis revealed low blood flow in uterine and umbilical arteries compared to that found in wild type pregnant mice. On the other hand, loss of mouse TTR function did not cause any pregnancy abnormalities in Ttr-/- mice. These observations in the PE placenta, cultured trophoblast cells and TTR transgenic mice indicate that TTR aggregation is an important causal contributor to PE pathophysiology.

Comparison of Diagnostic Values of Maternal Arginine Concentration for Different Pregnancy Complications: A Systematic Review and Meta-Analysis

Abnormal arginine metabolism contributes to the development of intrauterine growth restriction (IUGR), preeclampsia (PE), and gestational diabetes mellitus (GDM), which increase the health burden of mothers and induce adverse birth outcomes. However, associations between maternal arginine concentration and different pregnancy complications have not been systematically compared. The PubMed, ScienceDirect, and Web of Science databases were searched for peer-reviewed publications to evaluate the diagnostic value of plasma arginine concentration in complicated pregnancies. Standardized mean difference (SMD) of the arginine concentration was pooled by a random effects model. The results show that increased maternal arginine concentrations were observed in IUGR (SMD: 0.48; 95% CI: 0.20, 0.76; I2 = 47.0%) and GDM (SMD: 0.46; 95% CI: 0.11, 0.81; I2 = 82.3%) cases but not in PE patients (SMD: 0.21; 95% CI: −0.04, 0.47; I2 = 80.3%) compared with the normal cohorts. Subgroup analyses indicated that the non-fasting circulating arginine concentration in third trimester was increased significantly in GDM and severe IUGR pregnancies, but the change mode was dependent on ethnicity. Additionally, only severe PE persons were accompanied by higher plasma arginine concentrations. These findings suggest that maternal arginine concentration is an important reference for assessing the development of pregnancy complications.

Neonatal hypoglycemia in children with risk factors

Objective: The analysis of clinical-laboratory peculiarities and the dynamics of glycemia clarifying the terms of blood glucose stabilization during the early neonatal period in children having risk factors of the development of such state.Methods: Open, retrospective , continuous, single-center study was conducted. It was aimed at getting preliminary data that is important for planning further tactics of examining newborns having risk factors on hypoglycemia development (kids having large body weight at birth, children whose mothers have diabetes, newborns having intrauterine growth retardation).The target group of the survey included 522 newborns of both genders in the early neonatal period (from 0 to 7 days of life).Results: There is data on the frequency of first indicated hypoglycemia in newborns having risk factors of the development of such state, clinicallaboratory peculiarities, the dynamics of glycemia during early neonatal period, and also the period of blood glucose stabilization (the age of reaching normoglycemia). Neonatal hypoglycemia was detected in 40.2% of examined children. Laboratory manifestation during the first day of life was noticed 62.9% of cases with the further normalization of glucose level in blood in 24 hours in 73.3% of newborns. Significant reduction of blood glucose was observed in 54.8% of cases requiring hypoglycemia therapy with parenteral prescription of 10% glucose solution. Hypoglycemia jugulated against oral correction of 5% glucoses solution in 40.5 % of cases. 4.8% of children got the level of glucose stabilized after introduction of supplementary feeding.Conclusion: The results of the newborns having risk factors on hypoglycemia development (kids having large body weight at birth, children whose mothers have diabetes, newborns having intrauterine growth retardation) examinations are presented. The peculiarities of neonatal hypoglycemia are: the absence of a typical clinical symptoms among 89% of children. Asymptomatic course of hypoglycemia confirms the importance and necessity of glycemia monitoring in the early neonatal period in order to conduct timely and adequate therapy.

Women with Severe Anemia in Labor: Fetomaternal Outcomes

Background: Anaemia in pregnancy is the leading medical disorder in developing countries like India. Women with severe anemia in labor is a challenging situation for the obstetrician with increased maternal and perinatal morbidity and mortality. It has multifactorial etiology, Main cause of anemia in obstetrics is iron deficiency. There are specific risks for the mother like preterm labour pain, IUGR baby, preeclampsia, antepartum haemorrhage, sepsis etc and the fetus such as prematurity, lowbirth weight, birth asphyxia etc. Aim and Objectives: To determine the socio-demographic variables and also the maternal and perinatal outcomes of pregnant women admitted to labour room with severe anemia (Hb <7gm%) late in pregnancy. Results: It was seen that out of 50 severely anemic women, 82% had Hb between 4-7 gm% and 18% had Hb < 4gm%. Severe anemia is seen in 82% unbooked patients and only in 18% booked patients. There was increased incidence of preterm delivery, PPH, preeclampsia, eclampsia, mortality in anemic group as compared to non anemic group. Among the adverse fetal outcomes, there was increased incidence of intrauterine deaths, intrauterine growth restriction, NICU admission, low birth weight among the anemic group as compared to non anemic group. Conclusions: Severely anemic women reporting in labor had significantly high maternal and perinatal morbidity and mortality. Even a minor blood loss is much devastating for such patients. Extrapolating our observations, it can be said that a close vigilance, anticipation of complications and appropriate care and interventions during labor and puerperium will help in improving outcomes in these severely anemic women. Awareness and education on early antenatal bookings, regular iron intake and continuous antenatal care should be the goal in tackling anemia in pregnancy. Key words: Anaemia, Iron deficiency, Intrauterine growth retardation, prematurity, maternal outcome, neonatal outcome.

Co-expression analysis of placental genes in the search for key signaling pathways and biomarkers of the great obstetrical syndromes

Objective. To study the molecular mechanisms responsible for the development of diseases grouped within the great obstetrical syndromes (GOS) at the level of the transcriptome of human maternal placenta.Material and Methods. We gathered the results of genome-wide transcriptome studies of the human placental tissue using Gene Expression Omnibus (GEO) data repository for the following phenotypes: physiological pregnancy, preeclampsia (PE), premature birth, and intrauterine growth restriction (IUGR). Eleven data sets were selected and supplemented with our experimental data; a total of 481 samples of human placental tissue were included in the integrative analysis. Bioinformatic data processing and statistical analyses were performed in the R v3.6.1 software environment using the Bioconductor packages. The pooled dataset was used to search for common molecular targets for GOS via weighted gene co-expression network analysis (WGCNA). The functional annotation of genes and the resulting clusters was carried out with the DAVID database; protein-protein interaction network was built using the STRING software; and the hub genes for the network were identified using the MCC analysis with plugin cytoHubba in Cytoscape software 3.7.2.Results. We obtained a table of expression levels for 15,167 genes in 246 samples. Hierarchical clustering of this network allowed to find 55 modules of co-expressed genes in the group with PE, 109 modules in the group with PB, 75 modules in patients with IUGR, and 56 modules in the control group. The preservation analysis of co-expressed modules for the studied phenotypes suggested the presence of a common cluster comprising eight genes specific only for patients with PE and IUGR, as well as the module of 23 co-expressed genes typical only for patients with PB and IUGR. Protein-protein interaction network was built for these gene sets, and the SOD1, TXNRD1, and UBB genes were the central nodes in the network. Based on network topology evaluation with cytoHubba, six hub genes (rank ˂ 5) were identified as follows: SOD1, TKT, TXNRD1, GCLM, GOT1, and ACO1.Conclusion. The obtained results allowed to identify promising genetic markers for preeclampsia, intrauterine growth restriction, and miscarriage. Moreover, the study also made it possible to identify the most important overlapping molecular mechanisms of these diseases occurring in the placental tissue.

Prevalence of Iron Deficiency Anemia Among Pregnant Women in Zawia, Libya

Background: anemia is the most nutritional disorders affecting pregnant women particularly iron deficiency anemia IDA.IDA threatened the mother islife and considered as an established risk factor for intrauterine growth retardation, leading on too poor neonatal health and perinatal death. Objective: the aim of the study was to estimate the prevalence of IDA in Zawia city according to their hemoglobin level, age, and education. Methods and materials: the study was carried out in different centers in Zawia city, it was comprised 82 pregnant women aged 19-42 years, at various stage of pregnancy, out of 82 women 54 fulfilled the criteria, pregnant women who weren’t have known about their hemoglobin, they were excluded. The data collected by using of a questioner including 30 questions were asked to participants face to face. Data analysis: after the date is collected it classified and analyzed to determine the percentage of pregnant women suffering from iron deficiency anemia. The data analyzed by using of Microsoft excel (2013). Results: the prevalence of anemia in the present study was 85.18%, This prevalence was almost consistent with studies conducted in ZAWIA city over the last years, from the current study it is evidence that pregnant women had poor knowledge regarding main risk of IDA as well as poor practices for IDA prevention.