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COVID-19 is an ongoing pandemic and has been extensively studied. However, the effects of COVID-19 during pregnancy, particularly on placental function, have not been verified. In this study, we used blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate whether COVID-19 incidence during pregnancy has any lasting effects with respect to placental oxygenation. This is a case-control study, in which eight cases of singleton pregnancies before 30 weeks gestation with COVID-19 mothers were included. Placental oxygenation was evaluated using BOLD-MRI after 32 weeks of gestation. BOLD-MRI was consecutively performed under normoxia (21% O2), hyperoxia (100% O2), and normoxia for 4 min each. Individual placental time–activity curves were evaluated to calculate the peak score (peakΔR2*) and the time from the start of maternal oxygen administration to the time of peakΔR2* (time to peakΔR2*). Eighteen COVID-19-free normal pregnancies from a previous study were used as the control group. No significant differences were found between the two groups regarding maternal background, number of days of delivery, birth weight, and placental weight. The parameter peakΔR2* was significantly decreased in the COVID-19 group (8 ± 3 vs. 5 ± 1, p <.001); however, there was no significant difference in time to peakΔR2* (458 ± 74 s vs. 471 ± 33 s, p =.644). In this study, BOLD-MRI was used to evaluate placental oxygenation during pregnancy in COVID-19-affected patients. COVID-19 during pregnancy decreased placental oxygenation even post-illness, but had no effect on fetal growth; further investigation of the possible effects of COVID-19 on the fetus and mother is warranted. [ABSTRACT FROM AUTHOR]

Background: COVID19 is caused by a newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) that affects pregnant women equally to the general population. How SARS-CoV2 affects the mothers, the neonates and the placental pathology remain controversial. Objective: To explore the effects of maternal SARS-CoV2 infection on the neonates and placental pathology in comparison to those from the normal pregnancies. Study design: Maternal, neonatal and placental pathology data were collected from medical records between March and August 2020 from New York Presbyterian- Brooklyn Methodist Hospital. The data from a total 142 neonates and 101 placentas from SARS-CoV2 positive mothers were compared with those from SARS-CoV2 negative mothers. Results: There were 142 SARS-CoV2 positive mothers within the study group, and 43 (36%) of them showed various degrees of COVID19 related clinical symptoms including fever (13.8%), cough (5.7%), loss of taste/smell (anosmia)(5.6%), shortness of breath (2.4%), muscle ache (2.4%), headache (1.6%) and pneumonia (0.8%). A total 142 neonates were born to the SARS-CoV-2 positive mothers, and only 1 neonate tested positive for SARS-CoV2 in the first 24 h. Two additional neonates were initially tested negative in first 24 h, and later tested positive on day 7 and the 1 month visit, and all these neonates were asymptomatic and had no sequelae. There was no increase of pre-term labor and delivery or NICU admissions from SARS-CoV2 positive mothers. Examination of 101 placentas from SARS-CoV2 positive mothers and 121 placentas from SARS-CoV2 negative mothers revealed no increase of placental pathologic features. There were more vaginal deliveries and more meconium stain of fetal membranes from the SARSCoV2 positive mothers. Previous reports of more maternal vascular malperfusion and fetal vascular malperfusion were not demonstrated in our current data. Conclusion: Although SARS-CoV2 is a significant risk to the pregnant women (mothers) and general population, there is no increased risk for neonates. Vertical transmission is rare, and perinatal transmission can also occur. There is no increased frequency of placental abnormalities in both maternal and fetal circulation. [ABSTRACT FROM AUTHOR]

In the therapy of placenta-originated diseases during pregnancy, the main challenges are fetal exposure to drugs, which can pass through the placenta and cause safety concerns for fetal development. The design of placenta-resident drug delivery system is an advantageous method to minimize fetal exposure as well as reduce adverse maternal off-target effects. By utilizing the placenta as a biological barrier, the placenta-resident nanodrugs could be trapped in the local placenta to concentrate on the treatment of this abnormal originated tissue. Therefore, the success of such systems largely depends on the placental retention capacity. This paper expounds on the transport mechanism of nanodrugs in the placenta, analyzes the factors that affect the placental retention of nanodrugs, and summarizes the advantages and concerns of current nanoplatforms in the treatment of placenta-originated diseases. In general, this review aims to provide a theoretical basis for the construction of placenta-resident drug delivery systems, which will potentially enable safe and efficient clinical treatment for placenta-originated diseases in the future. [ABSTRACT FROM AUTHOR]

Proposing hysteroscopic morcellation (HM) as a surgical-therapeutic approach in the treatment of retained products of conception (RPOC) to prevent intrauterine adhesions (IUAs). Prospective analysis. A teaching and university hospital. Women with RPOC. Office -HM with 'Truclear 5 C'. Twenty-two consecutive patients presenting with trophoblastic residue retention after miscarriage and interruption of pregnancy or placenta remnants after cesarean section or delivery were enrolled. These women underwent office-HM with 'Truclear 5 C'. Primary outcomes were median time and rate of hospitalization. The quality of the specimen was also analyzed. A hysteroscopic second look for IUAs was performed. Mean procedure time was six minutes (SD ± 5). Tissue samples had a mean collection size 2.5 cm3+0.9. 38% of the samples had spotting or abnormal vaginal discharge. Dilatation of the cervical canal was not performed in any case. Second-look hysteroscopy did not show any de novo IUAs in any of the enrolled patients. In the hysteroscopic treatment of RPOC, HM is a valid choice in an office setting without the use of cervical dilatation. Removal of RPOC was uneventful in all cases, simple and carried out faster without any adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Villitis of unknown etiology (VUE) is an inflammatory placental lesion with immune-mediated pathogenesis, diagnosed by histopathological examination. It is one of the three placental lesions which tend to recur in subsequent pregnancies, the other two being chronic histiocytic intervillositis and massive fibrin deposition. The frequency of VUE and its association with maternal, obstetric and neonatal complications are variability reported in the literature. The aim of this study is to determine the frequency of VUE in the population studied and to observe the association of specific subtypes of villitis with clinical features, placental morphometric and microscopic parameters.Methods: Placentas where villitis was observed, were obtained from the pathology database from January 2013 to June 2018. VUE was graded as low grade (LG), high grade (HG) and basal villitis (BV) and subcategorized based on extent and cell type. Its association with selected maternal, neonatal and placental parameters was evaluated.Results: A total of 1603 placentas were received and 163 singleton placentas with villitis (10%) were reported. LG and HG villitis was observed in 58% and 25% cases respectively. Basal villitis was seen in 24% and pure basal villitis without involvement of parenchymal villi was seen in 16.6%. While there was near equal distribution of focal (n = 45) and multifocal (n = 50) LG villitis, diffuse HG villitis (n = 32) was more common than patchy HG villitis (n = 9). Overall villitis was more common in preterm pregnancies (59.5%) with most of them being basal villitis and low-grade villitis (64.2%, p value .029). None of the other maternal and neonatal parameters had any significance. Placental dimensions (length and breadth) showed a significant negative association with VUE, especially high-grade and multifocal low-grade villitis.Conclusion: VUE was a common finding in preterm births and its novel association with placental size opens avenues for further research on alternative mechanisms involved in the association between villitis, placental function and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

This study sought to assess the impact of COVID-19 on placental vasculature in the context of maternal symptomatology – comparing asymptomatic to symptomatic pregnant patients – and disease severity – comparing pregnant patients with mild, moderate, severe, and critical COVID-19 infection. PCR-confirmed COVID-19 positive pregnant patients in a single health system who delivered between 3/2020-5/2021 included. All patients had positive COVID test and delivered during the study period. Primary outcome was incidence of any vascular malperfusion on placental pathology. Secondary outcomes were FVM and MVM on placental pathology. Placental pathology compared between symptomatic (sCOVID) and asymptomatic (aCOVID) patients. Secondary analysis of symptomatic patients, comparing placental pathology between mild disease(mCOVID) and worse disease(moderate, severe, or critical-defined by 2020 NIH guidelines) (dCOVID), also performed. Of 112 patients, 53 (47%) had symptoms. Twenty-seven (24.1%) patients had evidence of vascular malperfusion; 26 (23.2%) had MVM. When comparing aCOVID and sCOVID patients, no difference in rate of vascular malperfusion identified, nor any differences in rates of FVM or MVM. Among sCOVID patients (n = 53), 39 (74%) had mCOVID and 14 (26%) had dCOVID (moderate n = 4, severe n = 9, critical n = 1). Patients with dCOVID had earlier median delivery GA (37.4wks vs 39.2wks, p = .03). No difference in latency from diagnosis to delivery seen between mCOVID and dCOVID groups (4.4 vs 3.0wks, p = .96). Twelve (30.8%) patients had vascular malperfusion on pathology, all had mCOVID (p = .02). Eleven (28.2%) mCOVID patients had MVM; no dCOVID patients had evidence of vascular malperfusion (p = .03). No difference in FVM was found between cohorts. Symptomatic COVID-19 infection did not impact placental vasculature differently than asymptomatic infection, even when stratifying by trimester of infection. Among pregnant patients with symptomatic COVID-19, mild disease was associated with placental vascular changes on the maternal side while severe disease was not. Further studies are needed to understand the implications of these findings. [ABSTRACT FROM AUTHOR]

Objective: Retained placenta is a leading cause of maternal hemorrhage. A history of retained placenta is a well-recognized risk factor for recurrence; however, recurrence risk pattern has not been previously described. We aimed to evaluate the longitudinal recurrence pattern of retained placenta in multiple consecutive deliveries.Methods: This is a retrospective computerized base study conducted at Shaare Zedek Medical Center, a university-affiliated hospital, between 2005 and 2018. Medical records of parturient who had at least one coded diagnosis of either retained partial or complete placenta were retrieved. The first delivery with retained placenta diagnosis was chosen as the index delivery. In order to account for dependency between deliveries of the same individual parturient, we used a multivariate binary logistic regression with generalized estimating equation (GEE) to calculate the individual recurrence risk, adjusted odds ratios (95% confidence interval).Results: During the study period, we identified 2177 parturient diagnosed with retained placenta in the index delivery and that had at least one subsequent delivery; overall 300 (13.8%) parturient had at least one subsequent event of retained placenta: 9.3% for the subsequent delivery and 6% in later deliveries. Induction of labor and epidural analgesia either in the index or in the subsequent delivery were found to be independently associated with recurrence 1.61 (1.16-2.24), 1.45 (1.10-1.90) and 1.46 (1.11-1.93), 1.82 (1.45-2.28), respectively. Complete and not partial retained placenta in the index delivery was also found to be independently associated with recurrence 4.90 (3.90-6.32).Conclusion: For the individual parturient, an event of retained placenta is a sentinel of the subsequent deliveries and has modifiable recurrence risks. [ABSTRACT FROM AUTHOR]

We aimed to examine the impact of maternal hypothyroidism on placental pathology and perinatal outcomes in singleton live births resulting from IVF, using medical records of IVF births between 2009 and 2017 at a tertiary hospital. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental features. Secondary outcomes included foetal, maternal, perinatal, and delivery complications. There were 1,057 live births, of which 103 (9.7%) and 954 (90.3%) were in the study and control groups, respectively. Patients in the study group were more likely to have diabetes mellitus, polycystic ovarian syndrome, gestational diabetes mellitus, and non-reassuring foetal heart rate (NRFHR) tracing during delivery. After adjustment for potential confounding factors, hypothyroidism was significantly associated with the bilobed placenta (aOR 4.1; 95% CI 1.2–14.3), retroplacental haematoma (aOR 2.4; 95% CI 1.2–4.9), decidual arteriopathy (aOR 2.0; 95% CI 1.2–4.1) and subchorionic thrombi (aOR 2.4; 95% CI 1.3–5.0). Additionally, there was a statistically significant relationship with NRFHR tracing. The incidence of acute chorioamnionitis and severe foetal inflammatory response was higher in the study group. In conclusion, the placental histopathology patterns of singleton IVF live births show that maternal hypothyroidism has a significant impact on adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

An adequately sized placenta at a suitable site with appropriate depth and centripetal progression of implantation are the major factors for optimal fetal development. The cytotrophoblasts surround the blastocyst fuses at the site of the uterine attachment. This forms a second layer of multinucleated syncytiotrophoblasts that constitutes the inner epithelial boundary of the chorionic villous against the intervillous space. In a normal pregnancy, extravillous cytotrophoblasts (EVT) invade and obstruct the spiral arteries and remodel them. Vacuoles in the syncytial cell layer fuse and develop the intervillous space. The inner cell mass (embryoblast) gives rise to the umbilical cord and the mesenchyme in the chorionic villi. Vasculogenesis starts with the formation of hemangioblastic cords in this mesenchyme. The trophoblastic cell columns anchor the placenta. A variety of molecular pathways participate in the placentation process. Placental morphogenesis occurs mainly through complex cellular interactions between the chorionic villous and the extravillous cytotrophoblasts. The formation of the normal structure of the chorionic villi, syncytiotrophoblast layer and vasculature is essential for placental function, hormone production, and regulation of fetal growth. At each stage of placental development, genetic variants, exposure to infection, poor vascular function, oxidative stress, or failure of normal development can all lead to abnormal formation resulting in the clinical complications of pregnancy such as fetal growth disorders, neonatal neurologic abnormalities, placental adhesions, and inflammatory problems as well as maternal disease such as preeclampsia. [ABSTRACT FROM AUTHOR]

In the current study, we sought to characterise the methylation haplotypes and nucleosome positioning patterns of placental DNA and plasma cell-free DNA of pregnant women with early-onset preeclampsia using whole genome bisulphite sequencing (WGBS) and methylation capture bisulphite sequencing (MCBS) and further develop and examine the diagnostic performance of a generalised linear model (GLM) by incorporating the epigenetic features for early-onset preeclampsia. This case-control study recruited pregnant women aged at least 18 years who delivered their babies at our Hospital. In addition, non-pregnant women with no previous history of diseases were included. Placental samples of the villous parenchyma were taken at the time of delivery and venous blood was drawn from pregnant women during non-invasive prenatal testing at 12–15 weeks of pregnancy and nonpregnant women during the physical check-up. WGBS and MCBS were carried out of extracted genomic DNA. Then, we established the GLM by incorporating preeclampsia-specific methylation haplotypes and nucleosome positioning patterns and examined the diagnostic performance of the model by receiver operating characteristic (ROC) curve analysis. The study included 135 pregnant women and 50 non-pregnant women. Our high-depth MCBS revealed notably different DNA methylation and nucleosome positioning patterns between women with and without preeclampsia. Preeclampsia-specific hypermethylated sites were found predominantly in the promoter regions and particularly enriched in CTCF on the X chromosome. Totally, 2379 preeclampsia-specific methylation haplotypes were found across the entire genome. ROC analysis showed that the area under the ROC curve (AUC) was 0.938 (95%CI 0.877, 1.000). At a GLM cut-off of 0.341, the AUC was the maximum, with a sensitivity of 95.6% and a specificity of 89.7%. Pregnant women with early-onset preeclampsia exhibit DNA methylation and nucleosome positioning patterns in placental and plasma DNA. Early-onset preeclampsia is a potentially dangerous condition that can have a profound impact on the health of both the expectant mother and her unborn child. This condition is particularly concerning because it's challenging to predict who may be affected using conventional methods such as monitoring blood pressure. In our research, we've developed an innovative, non-invasive approach to predict the onset of early preeclampsia. We do this by analysing the genetic material of the developing baby, which can be found in the mother's blood. Our method has shown remarkable accuracy in our testing populations, and its implications are substantial. By providing an early warning system, this breakthrough can benefit pregnant women immensely. It means that early-onset preeclampsia can be identified and addressed well before it becomes a serious health threat. This allows for timely medical interventions and treatments, significantly improving the well-being of both mothers and their precious little ones. [ABSTRACT FROM AUTHOR]

Uterine leiomyomata have been loosely associated with intrauterine fetal demise (IUFD), largely attributed to fetal growth restriction from cavitary distortion. We present two cases of IUFD in patients with non-distorting leiomyomata and pathologic placental findings of maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM). Case 1 details a 28w3d IUFD associated with large leiomyomata (largest 11.9 × 7.6 × 9.7 cm), post-partum deep vein thrombosis, and severe pre-eclampsia histologic features. Case 2 details a 25w2d IUFD associated with smaller leiomyomata (largest 3.1 × 3.0 × 3.3 cm). Both placentas demonstrated MVM, including parenchymal thrombi and accelerated villous maturity, and FVM, including avascular stem villi. As the placentas in both cases demonstrated findings consistent with altered placental perfusion, we posit that leiomyomata in these cases may have been associated with both maternal and fetal vascular malperfusion, ultimately contributing to fetal demise. [ABSTRACT FROM AUTHOR]

In-vitro-fertilization (IVF) is an independent risk factor for placenta previa (PP). Our aim was to study this link by comparing the clinical characteristics and placental histology of pregnancies complicated by PP in IVF versus unassisted pregnancies. A retrospective-cohort study of deliveries with PP between 2008 and 2021. Placental histology, obstetric and neonatal outcomes were compared between IVF and unassisted pregnancies. Included, were singleton deliveries complicated by PP at gestational weeks (GA) >24. A total of 182 pregnancies were included − 23 IVF pregnancies (IVF group) and 159 unassisted pregnancies (Control group). The control group was characterized by higher gravidity (p =.007) and parity (p <.001) and a trend of more past cesarean deliveries, whereas the IVF group- by a higher rate of nulliparity (p <.001) and diabetes mellitus (p =.04). The control group was characterized by a higher rate of placental weight below the 10th percentile (47.8 versus 13.9%, p =.001) and by a trend of a lower overall placental weight. No differences were noted in maternal and fetal vascular lesions. While PP in non-assisted pregnancies is probably associated with previous CDs, in IVF it is more "sporadic," and may complicate any index pregnancy. A lower placental weight was more prevalent in the control group, supporting the concept that pregnancies complicated by PP following IVF can be attributed to initial abnormal location of placentation, rather than an underlying pathological uterine segment of implantation. Nevertheless, IVF and unassisted pregnancies entail similar perinatal outcomes in cases of PP. [ABSTRACT FROM AUTHOR]

Ultrasound is key to evaluating placental function. However, traditional ultrasound examinations cannot evaluate the changes in the biomechanical properties of the placenta in vivo. As a non-invasive technique, shear wave elastography (SWE) can be used analyze the physiological and biomechanical properties of the placenta. Moreover, it can evaluate the pathological changes in early placental insufficiency in a more direct and sensitive manner. This study aimed to systematically introduce SWE in placental function evaluations. The terms 'placenta', 'ultrasound', and 'elastography' were searched on Pubmed, Embase, and CNKI databases (Apr 2023); this review was limited to results including placental sonoelastography. Twenty-six studies satisfied the inclusion criteria and were included in this review. Herein, we introduce the basic principle of SWE, analyze the factors affecting placental measurements, and summarize the prospects of clinical applications of SWE in the field of obstetrical diseases. The SWE technology demonstrates excellent clinical application value and research prospects in obstetrics, particularly in placental function evaluation, owing to its objective and repeatable quantitative operation. [ABSTRACT FROM AUTHOR]

Fetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma. This retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages. Nineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log2-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p <.001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients. Pregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics. [ABSTRACT FROM AUTHOR]

The identification of fetal growth disorders is an important clinical priority given that they increase the risk of perinatal morbidity and mortality as well as long-term diseases. A subset of small-for-gestational-age (SGA) infants are growth-restricted, and this condition is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathologies. During pregnancy, a "specialized" form of the glycocalyx—the "syncytiotrophoblast glycocalyx"—covers the placental villi. The purpose of this study was to determine whether the concentration of maternal plasma syndecan-1 can be proposed as a biomarker for fetal growth restriction. A cross-sectional study was designed to include women with normal pregnancy (n = 130) and pregnant women who delivered an SGA neonate (n = 50). Doppler velocimetry of the uterine and umbilical arteries was performed in women with an SGA fetus at the time of diagnosis. Venipuncture was performed within 48 h of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay. (1) Plasma syndecan-1 concentration followed a nonlinear increase with gestational age in uncomplicated pregnancies (R2 = 0.27, p <.001); (2) women with a pregnancy complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate-for-gestational-age fetus (p =.0001); (3) this difference can be attributed to fetal growth restriction, as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with an SGA fetus who had abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p =.00071; adjusted p =.0028). A trend toward lower syndecan-1 concentrations was also noted for SGA with abnormal uterine but normal umbilical artery Doppler velocimetry (p =.0505; adjusted p =.067); 4) among women with an SGA fetus, those with abnormal umbilical and uterine artery Doppler findings had a lower mean plasma syndecan-1 concentration than women with normal Doppler velocimetry (p =.02; adjusted p =.04); 5) an inverse relationship was found between the maternal plasma syndecan-1 concentration and the umbilical artery pulsatility index (r = −0.5; p =.003); and 6) a plasma syndecan-1 concentration ≤ 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus who had abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p <.001). Low maternal plasma syndecan-1 may reflect placental diseases and this protein could be a biomarker for fetal growth restriction. However, as a sole biomarker for this condition, its accuracy is low. [ABSTRACT FROM AUTHOR]

Introduction: The most popular model of preeclampsia (PE) is a two-stage one in which the first stage involves a decreased perfusion of the placenta and the second stage is characterized by maternal endothelial injury and dysfunction. This model seems to be more appropriate for early-onset PE, than for the late-onset disease, as in the case of the latter the event of reduced placental perfusion seems is less obvious. The aim of the study was to assess the possible correlations between the serum levels of soluble FMS-like tyrosine kinase 1 (sFlt-1) and the components of endothelial glycocalyx (EG), namely syndecan −1 (SDC-1) and hyaluronan (HA), as the markers of endothelial damage, in patients with early- and late-onset PE. Materials and methods: The study was conducted among 60 women in their late second and third trimester of the singleton pregnancy, including 20 patients with early-onset PE, 20 with late-onset PE, and 20 women with normal pregnancy, who served as the control group. All patients were hospitalized between 2015 and 2018 at the Division of Reproduction of Poznan University of Medical Sciences. The women in the control group were matched by gestational age with the patients in the study groups. Results: The median serum level of sFlt-1 was the highest in the patients with early-onset PE (3.53 (2.73–4.5) pg/ml) but it was not statistically different from the level in the patients with late-onset PE (3.14 (2.2–3.4) pg/ml). The mean serum level of SDC-1 also did not differ significantly between the two groups of patients with PE (6.17 ± 2.2 ng/ml in early-onset PE; 6.42 ± 2.2 ng/ml in late-onset PE). Both values of SDC-1 were significantly lower than that in the healthy pregnant women (11 ± 2.62 ng/ml, p < .001). The median concentrations of HA did not differ between patients with early- (236.6 (101.1–351.9) ng/ml) and late-onset PE (234.7 (46.8–324.2) ng/ml). However, the levels in these study groups were significantly higher than in the control group (113.9 (30.9–379.8) ng/ml, p < .001). There was no significant correlation found between the serum concentrations of sFlt-1 and both HA and SDC-1; however, such trend was noticed between the serum concentrations of sFlt-1 and HA in patients with early-onset PE, but not in those with the late-onset disease Conclusions: Evaluation of serum concentrations of HA in patients with PE was found to be more useful in the assessment of endothelial injury, compared to the assessment of SDC-1.The degree of EG damage was comparable in patients with early- and late-onset PE. The pathomechanism of the damage seems to be more sFlt-1 dependent in patients with early- onset PE than in the case of late-onset disease. The two-stage model of PE is more appropriate for early - onset PE, whereas the pathophysiology of the late-onset disease is rather more complex and heterogenous. [ABSTRACT FROM AUTHOR]

Objectives To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes.  Study design A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. Results Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. Conclusions cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients’ management. [ABSTRACT FROM AUTHOR]

Introduction: Placental villitis is characterized by the presence of inflammatory infiltrate in the placental villous. The objective of this study was to characterize in villitis of unknown etiology (VUE) of the human placentas the subpopulation of M1, important effector cells, and M2 macrophages, immunoregulatory cells. Methods: Sixteen cases of VUE and three control placentas were examined using immunohistochemistry with antibodies for CD3, CD68, CD11c, and CD163. Results: CD11c appeared predominantly in the inflamed villi when compared to the normal areas (p<.001). These cells corresponded to 41.2% of the macrophage population in the inflamed area and were mainly present inside the villi (36%). With regards to CD163, these cells tended to be in higher amounts in the inflamed villi when compared to CD11c and normal areas. Discussion: We conclude that the almost exclusive presence of M1 macrophages in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The greater amount of M2 in villitis and normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE. [ABSTRACT FROM AUTHOR]

Objective To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR). Methods A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study. Results Pregnancies with early-onset FGR were more associated with hypertensive disorders (p = .00) and placental vascular insufficiency, resulting in a high degree of umbilical artery Doppler involvement (p = .00) in a short period of pregnancy and higher rates of adverse perinatal outcomes (p = .00). The time of prenatal follow-up of early- and late-onset FGR cases was similar, but the degree of prematurity of the former made the evolution more unfavorable. Conclusion Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR. [ABSTRACT FROM AUTHOR]

Purpose Placental hypoxic-ischemic pathology is one of the common causes for adverse outcomes. But there is no commonly accepted evaluation system on specific morphological and histopathological measures of the placenta. Objective This study aims to systematically select several core placental hypoxic-ischemic measures that have a high prognostic relevance to child health. Methods We used data from the Collaborative Perinatal Project, a multicenter prospective cohort study that recruited over 55,000 pregnant women and followed their offspring to 7 years old. Women who had information on placental pathology and child outcomes were included. 57 placental measures considered to be relevant to hypoxia-ischemia were selected. Apgar score, intelligence quotient, preeclampsia, birth weight and subclinical neurology injuries were chosen as outcomes. The least absolute shrinkage and selection operator (LASSO) procedure as well as training and testing methods were used to select a more efficient and simpler placental hypoxic-ischemic measures that may have clinical implications. Results Of the 57 measures, 7 were selected as candidates by LASSO. Based on the training and testing methods, we retained placental measures with a higher odds ratio of child morbidity. We further narrowed down to four measures that had the highest prognostic relevance. They were: short cord length (ΣOR = 8.51), calcification of cut surface (ΣOR = 8.31), opaque membranes (ΣOR = 5.26), Hofbauer cells in terminal villi (ΣOR = 4.69). Conclusions Our four-measure system is relatively simple and closely related to the child health. It may be used as a novel placental hypoxic-ischemic evaluation criterion, and function as the first line tool for future research. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a serious pregnancy syndrome. Advanced maternal age (≥ 35 years old) is one of the major risk factors of PE and placental aging is considered to be related to this disease. However, the mechanisms underlying these phenomena remain obscured. Gene expression profiles of PE and non-PE placental samples were curated from the GSE75010 dataset. A diagnostic model was constructed and immune characteristics of PE subtypes were estimated. A total of 58 aging-related genes, which may be associated with PE, were identified. Among them, LEP and FLT1 may be key aging-related genes. Based on 5 top genes (PIK3CB, FLT1, LEP, PIK3R1, CSNK1E), a diagnostic nomogram for PE was built (AUC = 0.872 in the GSE75010 dataset). Three molecular subtypes were clustered, which had different immune and angiogenesis characteristics. The present study suggests the potential implications of aging-related genes in diagnosing PE. Diverse immune characteristics may be involved in the placental aging of PE. [ABSTRACT FROM AUTHOR]

Aim: The present paper intends in the first place to clarify the confusing terminology for describing the vascular pathology of the placental bed in relation to long-term risk of cardiovascular disease.Methods: Systematic review of relevant topics.Results: The maternal blood supply to the placenta is achieved by some 100 utero-placental spiral arteries with an outside diameter varying between 200 and 600 microns. Defective physiological changes of the myometrial segment of utero-placental spiral arteries and, particularly in preeclampsia associated to hypertensive disease, the presence of atherosclerosis in their proximal segment are a cause of obstructive vascular pathology. On the other hand, basal arteries which supply the inner myometrium and basal decidua are not affected by physiological change and maintain their musculoelastic structure. They can be identified by their external diameter of less than 120 microns. Acute atherosis is an aspecific vascular lesion that occurs in basal as well as spiral arteries inside, as well as outside, the placental bed in association with a variety of obstetrical conditions.Conclusions: An increased risk of future cardiovascular disease, should be linked to atherosis or, at a later stage, atherosclerosis of utero-placental spiral arteries, rather than to that of decidual basal arteries. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE), is a pregnancy-specific complication with the placental origin which associated with altered expression of angiogenic factors. Vascular Endothelial Growth Factor (VEGF), is a growth and hypoxia-induced factor which contributes to the regulation of various processes. The present study has investigated the association of the placental VEGF −634G/C (rs2010963), −1154G/A (rs1570360), and −2549 I/D (18bpindel) polymorphisms in the promoter region with VEGF mRNA expression in PE women and control group. Methods: This case-control study was performed on the placenta of 84 PE women and 103 controls after delivery. Genotyping of the VEGF polymorphisms was done by PCR or PCR, PCR-RFLP or sequencing methods. The mRNA expression levels were measured by Quantitative Real-Time PCR. Results: The relative mRNA expression of VEGF gene was significantly higher in PE women compared to controls. The relative mRNA expression of VEGF gene was significantly higher in women with −634CC genotype compared to CG + GG genotypes in PE women and total studied women but not in control women. However, there was no association between the placental VEGF −1154G/A and −2549 I/D polymorphisms and VEGF mRNA expression neither in PE nor in control groups. Conclusion: The current study found higher mRNA expression of placental VEGF gene in PE women. The mRNA expression of the placental VEGF gene has been up-regulated in the placenta of women with −634CC genotype. No association was found between the placental VEGF −1154G/A and −2549 I/D polymorphisms and VEGF mRNA expression. [ABSTRACT FROM AUTHOR]

Objective: To determine frequency, stage and grade of placental histologic acute maternal inflammatory response (MIR) and fetal inflammatory response (FIR) in meconium-stained amniotic fluid (MSAF) in our predominantly African-American population.Methods: Term placentas with MSAF (n = 310) were evaluated for MIR/FIR, including stage/grade, and compared with placentas with clear amniotic fluid (AF) (n = 250). MIR/FIR were also evaluated in thick compared to thin MSAF subgroups. Selected demographic and clinical features were compared.Results: MIR and FIR were present in 57.7 and 40.3% of the MSAF compared to 44.0 and 29.2% of the clear AF group, respectively (p = .001 and .008). MIR with FIR was present in 35.8% of the MSAF compared to 25.2% of the clear AF group (p = .008); however, there was no significant difference in frequency of MIR without FIR between groups. There was no significant difference in frequency of MIR/FIR in thick compared to thin MSAF; however, thick MSAF was associated with higher FIR stage compared to thin MSAF (29.2 versus 5.4%, p = .004). This association was not seen with MIR stage or MIR/FIR grade.Conclusions: Histologic MIR and FIR are frequent findings in MSAF. Thick MSAF is associated with higher FIR stage when compared to thin MSAF. [ABSTRACT FROM AUTHOR]

The main complication of the abnormally invasive placenta is massive bleeding, with transfusions required frequently. We aim to evaluate the impact of interdisciplinary management on transfusion practices in women with abnormally invasive placenta. Clinical outcomes of women with abnormally invasive placenta treated between 2011 and 2019 were reviewed, including transfusion frequency. Patients divided into three groups: group A (women treated before the introduction of interdisciplinary management), group B (women attended to by a fixed interdisciplinary group), and group C (women with no accreta prenatal diagnosis). Patients with prenatal diagnosis and attended by a fixed interdisciplinary group (group B) required fewer units of red blood cells to be prepared and transfused (median number of units, 0 versus 2 in group A and 3 in group C). The participation of an interdisciplinary group, with strict standards for transfusion, reduces the frequency of use of blood substitutes during the care of women with abnormally invasive placenta. [ABSTRACT FROM AUTHOR]

Introduction: Urinary tract injuries (UTI) are a frequent complication of morbidly adherent placenta (MAP) management. In this study, we aim to characterize the type of UTI that occurs and to define if their incidence varies after establishing a fixed interdisciplinary group for the protocolized management of patients with MAP.Methodology: All patients with confirmed MAP attended between 2011 and 2019 in our institution, were included. We analyzed the effect of a change in the surgical protocol including rigid ureteral catheters, vesicouterine dissection before hysterotomy and interdisciplinary planning, in the bladder or ureteral injuries incidence.Results: The study included 65 women. UTI was identified in 27.7% of patients and was associated with a greater volume of blood loss, transfusion requirement, hospital stay, and the need for additional surgeries. There was a high frequency of UTI in patients without protocolized management. The use of rigid ureteral catheters and retrovesical dissection before hysterotomy were associated with a less ureteral injury.Conclusions: Developing expertise among the members of the surgical team is essential to improve results. Using rigid ureteral catheters, performing retrovesical dissection before hysterotomy, and performing less extensive surgeries in selected patients are associated with a low frequency of ureteral injuries. [ABSTRACT FROM AUTHOR]

Objective: Examine the association between placental inflammation and neonatal infections, and 25OH vitamin D (25OH D) levels at birth among very low birth weight infants (VLBWI).Study Design: Serum 25OH D levels were measured in 89 VLBWI (≤1250 g) and 47 mothers on day one, and in 78 infants on day 21. Placentas were examined for maternal and fetal inflammation. Infants were divided into deficient (≤10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D levels on day 1.Results: Mean ± SD maternal levels of 25OH D (21 ± 9 ng/ml) correlated with infants' levels (15 ± 8 ng/ml), (p < .001). 25OH D levels were lower in deficient (32/89) than in adequate group (8 ± 2 versus 20 ± 7 ng/ml, p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001). Univariate analyses showed no differences between infant groups in maternal or fetal inflammation, or neonatal infections (p > .05). Logistic regression analyses revealed no association between deficient 25OH D levels and the odds of maternal or fetal inflammation or other infections. Levels of 25OH D did not correlate with severity of placental inflammation.Conclusions: Deficient levels of 25OH D at birth are not associated with the occurrence of placental inflammation or neonatal infections among VLBWI. [ABSTRACT FROM AUTHOR]

Objective: Multiparas differ from nulliparas by delivering larger babies with larger placentas and by having a lower risk of developing placental syndromes. We postulate that these differences result from a different initial course of placental vascular development.Study Design: We measured placental flow index (FI), vascularization index (VI) and placental volume by 3D power Doppler and obtained blood samples at 8, 10 and 12 weeks pregnancy in 34 healthy nulliparous and 16 multiparous women with an uneventful pregnancy.Results: Between 8 and 12 weeks multiparas differed from nulliparas in a more rapid initial rise in FI, a higher angiopoietin-2 (ang2) level at eight weeks and no decline in the VEGF/sVEGF-R ratio. Nevertheless, at 12 weeks the FI and placental volume were indistinguishable between both study groups.Conclusions: These results combining serially measured placental vascularization, placental volume and circulating angiogenetic factors show initial differences in placental development, that howeve, did not maintain till the end of first trimester. The results support the concept that early placental vascular development differs between nulliparas and multiparas. Nevertheless, it is unclear whether these differences contribute to the development later on in pregnancy of intergroup differences in birthweight and incidence of placental syndromes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate whether the Serum Netrin-1 and Urinary KIM-1 (Kidney Injury Molecule-1) levels are associated with the detection of preeclampsia. A total of 90 patients, including 36 normal pregnant women, 29 patients with nonsevere preeclampsia and 25 patients with severe preeclampsia, were included in this study. Maternal serum Netrin-1 and Urinary KIM-1 levels were measured by using an enzyme-linked immunosorbent assay (ELISA). The results showed that the Levels of Netrin-1 and KIM-1 were statistically higher in women with preeclampsia as compared with normal pregnant women. Furthermore, the Netrin-1 level in women with severe preeclampsia was significantly higher than nonsevere preeclamptic women. inconclusion the current study showed that Maternal serum level of Netrin-1 and Urinary level of KIM-1 can be used as early biomarkers for the detection of preeclampsia. What is already known on this subject? Preeclampsia is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks' gestation. Netrin-1 was found to promote angiogenesis. Alteration of placental angiogenesis in early pregnancy is a well-known reason for placental dysfunction such as preeclampsia. Kidney injury with proteinuria is a characteristic feature of preeclampsia. Urine KIM-1 is the most potential biomarker for renal injury in preeclampsia. Due to these facts, we aimed to investigate the role of maternal serum Netrin-1 and Urine KIM-1 levels in preeclampsia presence and severity. What the results of this study add? A significant relationship between Netrin-1 and KIM-1 levels with preeclampsia. What the implications are of these findings for clinical practice and/or further research? Based on these findings, we concluded that increased levels of Netrin-1 and KIM-1 are associated with severe preeclampsia. [ABSTRACT FROM AUTHOR]

Severe hemorrhage is a major concern during operative procedures for abnormally invasive placenta (AIP). We reviewed published literature with the objective to provide evidence of blood loss with the most common treatment options for AIP. We selected 54 articles that fulfilled the inclusion criteria. Cesarean hysterectomy, with or without occlusion balloons in the internal iliac arteries, was the treatment associated with the greatest blood loss. Major blood loss was also associated with the placenta left in situ (reported in 3 of 10 articles), and with uterine artery embolization (reported in 3 of 15 articles). The best outcomes were seen for cesarean hysterectomy with balloon occlusion of the common iliac arteries (CIA; 9 patients, including 1 with major blood loss), balloon occlusion of the abdominal aorta (27 patients, no major blood loss) and conservative surgery (99 patients, including one with major blood loss). In conclusion, cesarean hysterectomy with balloon occlusion of the CIA or abdominal aorta, and conservative treatments seem to have the best outcomes. However, our results are based on a small number of articles. Hence, it is necessary to have available more reports on the outcomes of these treatments, to arrive at a more definitive conclusion. [ABSTRACT FROM AUTHOR]

This study evaluated the surgical and neonatal outcomes of 71 patients diagnosed with placenta accreta before caesarean section with or without placement of a prophylactic abdominal aorta balloon catheter. This study took place at our hospital from January 2013 to May 2015. Thirty patients had a prophylactic balloon catheter inserted (balloon group), and 41 patients did not receive the intervention (control group). The mean estimated blood loss and decrease in haemoglobin after surgery was significantly lower in the balloon group than in the control group. No significant difference was found in duration of operation, transfusion, or percentage requirement of caesarean hysterectomy. The incidence of catheterisation-related complications was 3.3%. One patient had pain in her right leg, caused by an ultrasound-confirmed haematoma in the front wall of the right common femoral artery. No significant difference was found in the rate of surgery-related complications and neonatal outcomes between the groups. Prophylactic placement of an infrarenal abdominal aorta balloon catheter in patients with placenta accreta can effectively reduce intraoperative haemorrhage, without causing any obvious adverse maternal or neonatal outcomes.Impact statementProphylactic placement of endovascular balloon catheters for controlling intraoperative haemorrhage in women with placenta accreta has been a topic of debate for nearly 2 decades. The most common type of occlusion is internal iliac artery balloon occlusion, only a few studies have focused on intraoperative aortic balloon occlusionThis retrospective case-control study included relatively large number of cases and the result shown this technique can effectively reduce intraoperative haemorrhage in patients with placenta accreta, without causing any obvious adverse maternal or neonatal outcomes.It provides another safe and effective method for intraoperative haemorrhage control and even uterine preservation. [ABSTRACT FROM PUBLISHER]

This prospective cohort study aimed to evaluate the role of premature placental calcification in adverse pregnancy outcomes and identify its associated potential risk factors. We consecutively enrolled 293 women who presented to three academic medical centres from September 2011 to March 2013. Participants underwent transabdominal sonographies between 28–36 weeks of gestation in an attempt to determine placental maturity. We compared maternal and foetal outcomes between two groups of women, those with grade III placenta (n = 69) and those without grade III placenta (n = 224). Passive smoking was the only predictor of early placental calcification. There were more abnormal Doppler, low birth weight (LBW) and caesarean section (CS) deliveries observed in the preterm calcification group. No definite relationship existed between maternal hypertension (HTN), diabetes and other medical diseases with placental calcification. In conclusion, umbilical artery (UA) resistance index (RI) and absent or reversed end-diastolic velocity (AREDV) were observed more often in preterm placental calcification. Serious antepartum follow-up should be advised for these mothers.Impact Statement • Placental calcification is a physiological phenomenon but normally, a grade III placenta is not frequently found until 36 weeks of gestation (so is called preterm placental calcification – PPC). There is currently a lack of consistent evidence on the clinical significance of PPC and pregnancy outcome. The present study was designed to evaluate the role of PPC in adverse pregnancy outcomes. • In our study, although none of the pregnant women were smokers, we found that passive smoking was the only predictor of PPC. Abnormal umbilical artery Doppler waveforms considerably and absent end diastolic velocity pattern significantly were observed more often in the PPC group. • We observed that PPC can be a landmark for high-risk pregnancy and an alarm sign for placental dysfunction. So, close antepartum follow up should be advised for these mothers. Regular and frequent foetal wellbeing tests should be done to prevent pregnancy complications. Certainly larger and more extensive study can provide more valid results. [ABSTRACT FROM PUBLISHER]

Objective: To explore the changes of serum, umbilical vein, placental irisin level, and the correlation between irisin level and relevant indicators in pregnant women with intrahepatic cholestasis of pregnancy (ICP), so as to provide a new perspective for in-depth studies on the causes and treatment of ICP.Methods: This cross-sectional case-control study method, the serum, umbilical venous blood irisin, liver, kidney function, lipid metabolism, and other indicators of 108 normal pregnant women, 64 patients with mild ICP, and 39 patients with severe ICP were compared, and the changes in the levels of oxidative stress and irisin were observed by dihydroethidium staining and immunohistochemistry.Results: The level of placental oxidative stress in severe ICP group and mild ICP group was significantly higher than that in normal pregnant women group, and the mild ICP group was significantly higher than that in severe ICP group (p < .05); the concentration of irisin in umbilical vein was significantly lower than that in peripheral blood; the serum irisin of normal pregnant women (918.51 ± 159.90 pg/ml) was significantly lower than that of pregnant women with mild ICP (1030.05 ± 137.98 pg/ml) and pregnant women with severe ICP (1094.34 ± 154.35 pg/ml). The concentration of irisin in umbilical vein blood of pregnant women with severe ICP (858.78 ± 97.42 pg/ml) was significantly higher than that of normal pregnant women (595.33 ± 162.70 pg/ml) and those with mild ICP (648.82 ± 164.81 pg/ml) (p < .05). Irisin was expressed in placental tissues of normal pregnant women group, mild ICP group and severe ICP group, and the differences were statistically significant in expression intensity of the three groups (χ2 = 19.959, p < .05). The irisin expression intensity in the ICP group was higher than that in the control group, and the irisin expression intensity in the ICP group was higher than that in the ICP group (β = 0.292; t = 3.063; p < .05). At the best cutoff level of 989.168 pg/ml, irisin accurately predicted ICP [AUC = 0.622 (95%CI 0.543-0.701, p < .05)] with sensitivity and specificity rates of 60.9 and 40.1%, respectively.Conclusion: Irisin can reduce the level of oxidative stress and improve lipid metabolism in ICP patients during the pathophysiological process of ICP, and it is possible to become a new auxiliary factor of ICP diagnosis and indexing. [ABSTRACT FROM AUTHOR]

This study aims to investigate the prevalence of depression and impaired sexual function following the hysterectomy in Iran. This study was performed as a retrospective cohort study, from August 2017 to August 2018. Fifty-two patients with a cesarean hysterectomy and 52 with cesarean section were considered as the cases and controls, respectively. Depression and sexual function were assessed 3–6 months following the surgery in both cases and controls. Depression was evaluated by using Beck Depression Inventory (BDI) questionnaire-II-Persian. Sexual function was assessed using the Female Sexual Function Index (FSFI). The average BDI in cases was 15.37 ± 7.6 and in controls was 13.06 ± 6.7. Mild to moderate depression was detected 57.3 percent of whom with hysterectomy and 36.5 percent of whom with C/S, the BDI sum score did not differ significantly between cases and controls (p =.096). The FSFI in cases was 20.06 ± 6.96, and controls was 21.7 ± 9.83 without any significant difference (p =.364). The depression had not been significantly different between women who underwent hysterectomy and were not following 3–6 months after surgery. Furthermore, both groups had impaired sexual function after the surgery. [ABSTRACT FROM AUTHOR]

According to the Developmental Origin of Health and Disease (DOHaD), intrauterine exposure to adverse environments can affect fetus and birth outcomes and lead to long-term disease susceptibility. Evidence has shown that neonatal outcomes and the timing and severity of adult diseases are sexually dimorphic. As the link between mother and fetus, the placenta is an essential regulator of fetal development programming. It is found that the physiological development trajectory of the placenta has sexual dimorphism. Furthermore, under pathological conditions, the placental function undergoes sex-specific adaptation to ensure fetal survival. Therefore, the placenta may be an important mediator of sexual dimorphism in neonatal outcomes and adult disease susceptibility. Few systematic reviews have been conducted on sexual dimorphism in placental development and its underlying mechanisms. In this review, sex chromosomes and sex hormones, as the main reasons for sexual differentiation of the placenta, will be discussed. Besides, in the etiology of fetal-originated adult diseases, overexposure to glucocorticoids is closely related to adverse neonatal outcomes and long-term disease susceptibility. Studies have found that prenatal glucocorticoid overexposure leads to sexually dimorphic expression of placental glucocorticoid receptor isoforms, resulting in different sensitivity of the placenta to glucocorticoids, and may further affect fetal development. The present review examines what is currently known about sex differences in placental development and the underlying regulatory mechanisms of this sex bias. This review highlights the importance of placental contributions to the origins of sexual dimorphism in health and diseases. It may help develop personalized diagnosis and treatment strategies for fetal development in pathological pregnancies. [ABSTRACT FROM AUTHOR]

Abnormal placentation is a potential cause of maternal morbidity and mortality from massive postpartum bleeding. The objective of this study was to investigate the efficacy of occlusive balloons when used as an adjunct to surgery in reducing blood loss and transfusion requirements. A retrospective study of 42 patients was performed involving consecutive cases of abnormal placentation who delivered with either conventional surgery with preoperatively placed occlusive balloons or conventional surgery alone. No differences were noted between the control group and the group of patients who had occlusive balloons with regard to estimated blood loss (P = 0.767), packed red blood cells transfused (P = 0.799), amount of crystalloids infused (P = 0.435), total procedure duration (P = 0.076), and length of ICU stay (P = 0.315) or total hospital stay (P = 0.254). Prophylactic intravascular balloon catheters did not benefit women with abnormal placentation when compared with conventional surgery alone. [ABSTRACT FROM AUTHOR]

Chronic histiocytic intervillositis of the placenta (CHI) shows monocytic/histiocytic infiltration of the intervillous space. Placental malaria has a CHI-like histopathology and induces an aberrant expression of Toll-like receptors (TLR) 3, 7–9. We hypothesized that, similar to placental malaria, CHI could be associated with increased TLR expression. TLR1-10 and other inflammation-associated factors were analyzed by real-time PCR and immunohistochemistry. A total of 31 formalin-fixed and paraffin–embedded placenta samples were evaluated: CHI (n = 9), and for control purposes, villitis of unknown etiology (VUE, n = 8) and placentas without inflammation (n = 14). CHI shows increased expression of monocytic TLR1, a receptor which is involved in bacterial lipopolysaccharide (LPS)-induced inflammation. This could indicate a TLR1-mediated immune mechanism in the placenta (e.g. triggered by transient, clinically inapparent maternal bacteraemia) which leads to massive monocytic/histiocytic accumulation in the intervillous space. The increased expression of TLR1 with no increased expression of TLR3 and TLR7-9 is different from that in malaria. [ABSTRACT FROM AUTHOR]

Objective: To investigate histopathological placental lesions and adverse neonatal outcomes by Pre-eclampsia (PE) with Gestational Diabetes Mellitus (GDM).Methods: This was a retrospective cohort study of pregnancies with PE delivered between 1 January 2012 to 1 January 2014. Pregnant women with PE were recruited, and divided into PE with GDM (PE + GDM) group (n = 278) and PE without GDM (PE - GDM) group (n = 586). We compared the placental pathology and neonatal outcomes between the two groups.Results: The (PE + GDM) group was significantly associated with high placenta weight (534.8 ± 124.1 vs 519.3 ± 132.3 g, p = .011), the large diameter of the placenta (17.8 ± 2.2 vs 16.2 ± 2.7 cm, p = .016) than (PE - GDM) group. The incidence of chorioamnionitis in (PE + GDM) group was significantly higher than (PE - GDM) group [48.9% (136/278) vs 41.5% (243/586), p = .028], whereas there were no significant differences in umbilical cord length and infarction between the two groups. The (PE + GDM) group had a higher rate of prematurity [44.9% (125/278) vs 39.9% (234/586), p = .042] than (PE - GDM) group, in (PE + GDM) group the incidence of LGA [15.1% (42/278) vs 1.0% (6/586), p = .034], RDS [18.7% (52/278) vs 9.2% (54/586), p = .011] and hyperbilirubinemia [10.7% (30/278) vs 1.0% (6/586), p = .038] were higher than (PE - GDM) group.Conclusions: GDM increased the offspring's complication in pregnancy with PE, the potential mechanism might be that GDM increased the placenta inflammation. [ABSTRACT FROM AUTHOR]

Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding. [ABSTRACT FROM AUTHOR]

Introduction: In this prospective multicenter study, we aimed to describe (1) the outcome of pregnancy in the case of previous chronic histiocytic intervillositis (CHI), (2) the immunological findings and associated diseases, (3) the treatments, and (4) the factors associated with pregnancy loss. Methods: We prospectively included all patients with a prior CHI with ongoing pregnancy between 2011 and 2013. Results: Twenty-four women (age 34 ± 5 years) were included in this study. An autoimmune disease was present in seven (29%) cases. Twenty-one prospective pregnancies were treated. The number of live births was more frequent comparatively to the previous obstetrical issues (16/24 versus 24/76; p = 0.003). Most of the pregnancies were treated (88%), whereas only 13% of previous pregnancies were treated ( p < 0.05). No difference was found with respect to the pregnancy outcome in the different treatment regimens. In univariate analyses, a prior history of intrauterine death and intrauterine growth restriction and the presence of CHI in prospective placentas were associated with failure to have a live birth. Discussion: In this multicenter study, we show the frequency of the associated autoimmune diseases in CHI, as well as the presence of autoantibodies without characterized autoimmune disease. The number of live births increased from 32% to 67% in the treated pregnancies. Despite the treatment intervention, the risk of preterm delivery remained at 30%. Last, we show that the recurrence rate of an adverse pregnancy outcome persisted at 30% despite treatment intervention. Conclusion: CHI is associated with high recurrence rate and the combined regimen seems to be necessary, in particular, in the presence of previous intrauterine death. [ABSTRACT FROM AUTHOR]

Purpose of the article: Placental accreta spectrum (PAS) is the most dangerous iatrogenic complication of cesarean potentially leading to massive intra-partum haemorrhage and death. Despite this, identification of near miss cases of PAS has not been consistently reported in the published literature. The aim of this systematic review was to explore prenatal and surgical characteristics of near miss cases of PAS disorders.Materials and methods: Medline, Embase, CINAHL, SciELO, and Cochrane databases were searched. Only studies including near miss cases of PAS disorders in which a detailed description of the clinical course, severity of placental invasion, role of prenatal imaging, and surgical management were considered eligible for the inclusion in the present systematic review. Random-effect meta-analyses of proportions were used to pool the data.Results: Thirty-four studies were included in the systematic review. The incidence of placenta accreta, increta, and percreta in near miss cases of PAS disorders was 0% (95% CI 0-24.6), 17.3% (95% CI 8.4-28.6) and 82.7% (95% CI 71.4-91.6). S1 invasion, defined as invasion in the upper posterior bladder wall was present in none of the near miss cases of PAS while all included cases showed S2 invasion. Prenatal imaging, either ultrasound or magnetic resonance imaging, detected invasive placenta in 54.4% (95% CI 41.0-67.5). Clinical symptoms occurred in 65.3% (95% CI 52.1-77.4) of near miss cases of PAS before surgery, while the corresponding figures for symptoms occurring during and after surgery were 65.5% (95% CI 52.2-77.5) and 50.0% (95% CI 36.5-63.5) of cases, respectively. Invasion in the inferior part of the lower uterine segment, posterior bladder and parametria was associated with a high risk of morbidity.Conclusion: Near miss cases of PAS are commonly associated with posterior bladder or parametrial invasion and placenta percreta. Further studies are needed in order to identify women affected by PAS disorders at high risk of surgical complications. [ABSTRACT FROM AUTHOR]

Introduction: Beginning in 2017, multiple stakeholders within the Southwest Texas Regional Advisory Council for Trauma collaborated to incorporate cold-stored low-titer O RhD-positive whole blood (LTO + WB) into all phases of their trauma system, including the prehospital phase of care. Although the program was initially focused on trauma resuscitation, it was expanded to included non-traumatic hemorrhagic shock patients that may benefit from whole blood resuscitation. Case Report: We report the case of a patient with severe maternal hemorrhage secondary to placenta accreta who received a prehospital transfusion of LTO + WB. We believe this to be the first reported case of post-partum hemorrhage resuscitated out of hospital with whole blood. Discussion: This case highlights the potential benefits of a prehospital whole blood program as well as the controversy surrounding a LTO + WB program that includes females of childbearing age. [ABSTRACT FROM AUTHOR]

Introduction: After a small-for-gestational-age (SGA) birth, recurrence of placenta-mediated pregnancy complications (PMPCs) is a cause for anxiety when contemplating another pregnancy. We sought to identify factors potentially associated with this recurrence.Material and methods: This retrospective single-center observational study was conducted in a tertiary maternity unit between 1 January 2010 and 31 December 2017. We included all women having experienced a non-syndromic SGA birth and who were subsequently monitored for at least one other pregnancy in our institution. PMPCs were defined as recurrent SGA births, three consecutive first-trimester miscarriages, or preeclampsia.Results: Ninety-four women were included over a 7-year study period. Recurrent PMPCs were recorded in 30 (32%) cases, of which 29 featured recurrent SGA births. None of the following characteristics were significantly associated with recurrence: presence of preeclampsia during the initial pregnancy (six [20%] versus 25 [39%] cases in the recurrent PMPCs and non-recurrent PMPCs groups, respectively; p = .11), results of the histopathologic placental examination or thrombophilia screen, or implemented treatment during subsequent pregnancies.Conclusions: PMPCs recur frequently. No risk factor for recurrence was identified in our study. Results of etiologic assessments and treatments implemented after an initial SGA birth should therefore not modify level of clinical and ultrasound monitoring provided during subsequent pregnancies.Rationale: Recurrence of placenta-mediated pregnancy complications is a cause for anxiety when contemplating another pregnancy. We did not identify any risk factor after an initial small-for-gestational-age birth in our study; surveillance should therefore not be modified by the etiologic assessments' results. [ABSTRACT FROM AUTHOR]

Patients of abnormally invasive placenta (AIP) undergoing caesarean delivery are at increased risk of haemorrhage. Conventional management includes piecemeal removal of placenta or placenta left in situ. However, they often require hysterectomy after delivery. Post-delivery prophylactic uterine artery embolisation (UAE) can help reduce morbidity and preserve fertility. We created an adjoining operating theatre and catheter lab (OT/CL complex). This is a retrospective case control study in which 37 patients of AIP were evaluated. Sixteen subjects (cases) had UAE immediately after caesarean delivery, and 21 subjects (controls) had usual care with traditional methods of controlling postpartum haemorrhage and hysterectomy where required. The hysterectomy rate (18.7% vs. 85.7%), mean duration of hospital stay (6.8 ± 2.6 vs. 13.9 ± 8.1) and number of units of blood transfusion required were significantly less in the case group as compared with controls. UAE is an effective conservative treatment along with caesarean delivery in patients with AIP.Impact statementWhat is already known? AIP is associated with high rates of PPH, maternal morbidity and mortality and need for hysterectomy after delivery. UAE has been advocated to preserve fertility and reduce PPH in these patients along with caesarean delivery.What doesthe study add? We created an adjoining operating theatre and catheter lab (OT/CL complex) in a tertiary care centre and managed these patients with prompt UAE after caesarean delivery with team approach. We have shown significant reduction in morbidity and hospital stay with this coordinated management.What are the implications for clinical practice and/or further research? UAE with caesarean delivery is a preferred mode of delivery for patients of AIP. These patients should be diagnosed and referred to tertiary care centres with such facilities electively so as to provide optimal care to these patients. Cooperation between interventionist and obstetrician and adjoining availability of OT and catheter lab can further help in reducing the time to embolisation after delivery. A hybrid operating theatre with digital subtraction angiography (DSA) facilities would be ideal for the management of such patients. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia is a systemic inflammatory disorder and a major cause of maternal and fetal mortality. Fractalkine (CX3CL1) is a member of the chemokine family with multiple functions in the organization of the immune system. It is up-regulated in inflammatory disorders. During inflammation, fractalkine enhances tissue destruction and inflammatory cell invasion. We aimed to investigate the alteration of fractalkine in the placental tissues of pregnant women with preeclampsia and the correlation of this alteration with clinicopathological variables.Materials and methods: Alteration of fractalkine in placental tissue specimens was determined immunohistochemically in 84 pregnant women: 33 women with mild preeclampsia, 19 women with severe preeclampsia, and 30 women with normal pregnancy. Preeclampsia was diagnosed using current guidelines of the American College of Obstetricians and Gynecologists.Results: Pregnant women with mild and severe preeclampsia revealed significantly higher fractalkine expression in syncytiotrophoblast cells than in the normotensive group (p = .0051 and .0001, respectively). The expression of fractalkine in preeclampsia was positively correlated with clinical parameters including the presence of intrauterine growth restriction, systolic and diastolic blood pressure, and 24-h urine protein, whereas it was negatively correlated with plasma albumin levels and placental weight. Additionally, the pathological changes in the placenta-including the presence of syncytiotrophoblast basement membrane thickening, increased number of syncytial knots, and vascularization of terminal villi were significantly correlated with fractalkine expression in pregnant women with preeclampsia.Conclusions: Overexpression of fractalkine in pregnant women with preeclampsia, as well as the correlation between fractalkine expression and poor pregnancy outcomes and placental histopathological changes may be associated with the underlying mechanisms of preeclampsia. [ABSTRACT FROM AUTHOR]

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Purpose: Vitamin D deficiency may be a main causative agent in the pathogenesis of preeclampsia (PE). The actions of the active form of vitamin D are mediated via the vitamin D receptor (VDR), which is expressed in numerous organs including placenta. Therefore, we evaluated the potential relationship between maternal and placental VDR polymorphisms and the predisposition to PE in an Iranian population. Methods: This case–control study surveyed 152 PE and 160 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal and placental VDR Fok1 rs2228570, Bsm1 rs1544410, Taq1 rs731236, and Apa1 rs7975232 polymorphisms. Results: The maternal but not placental VDR FokI Ff genotype, was significantly lower in PE women (P =.02 and P =.06, respectively). The maternal and placental VDR FokI polymorphism was associated with lower PE risk in the dominant model (Ff+ff vs. FF) and these genotypes could decrease PE risk (OR, 0.5 [95% CI, 0.3–0.8], P =.007 and OR, 0.5 [95% CI, 0.3–0.9], P =.02, respectively). The haplotype analysis revealed that the maternal and placental TABf haplotype may lead to decreased risk of PE. In addition, the placental TABF haplotype was associated with higher risk of PE. No relationship was observed between PE susceptibility and the maternal and placental VDR Bsm1, Taq1 and Apa1 polymorphisms. There was also no relationship between the maternal and placental VDR polymorphisms and PE severity. Conclusions: the maternal and placental VDR FokI variant was associated with decreased risk of PE in the dominant model. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the phenotype and function of NKT cells and the effect of NKT cells on the functions of vascular endothelial cells. The study included 30 pregnant women with hypertension and 20 pregnant women with normal delivery. Peripheral blood and placental tissues were collected from all patients and control subjects. Lymphocytes were isolated from peripheral blood and tissues. NKT cell ratio, expression of surface receptors and expression of effector molecules were detected by flow cytometry. Culture supernatant of NKT cells was collected and co-cultured with human umbilical vein endothelial cells (HUVECs). Proliferation was determined by CCK-8 assay, and migration, by transwell assay. The results showed elevated ratios of NKT and NK cells in peripheral blood and placental tissues from women with pregnancy-induced hypertension (PIH) compared with women with normal pregnancies. The expression of NKp30, NKG2D and NKG2A receptors on the surface of NKT cells from women with PIH was altered: the ratio of CD4+ NKT cells was increased but the ratio of CD8+ NKT cells was decreased. The ratios of GranB+ NKT cells in peripheral blood, IFN-γ-positive T cells in placental tissues and IL-17-positive NKT cells in both peripheral blood and placental tissues were elevated in PIH patients. The present study demonstrated that the ratio and activity of NKT cells from peripheral blood and placental tissues of women with PIH were elevated. In addition, NKT cells from peripheral blood of PIH patients inhibited the proliferation and migration of vascular endothelial cells by secreting IL-17. [ABSTRACT FROM AUTHOR]

Objective: To evaluate if placental histopathological changes of vascular insufficiency correlate with circulating angiogenic factors in patients with preeclampsia. Materials and methods: Subjects were selected from a previous prospective cohort study of preeclampsia based on the availability of plasma anti-angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and placental histology specimens. Preeclamptic patients were divided into two groups based on plasma levels of these factors described as a ratio: anti-angiogenic preeclampsia with sFlt1/PlGF ratio ≥85 and normal angiogenic preeclampsia with sFlt1/PlGF < 85. The placental lesions of vascular insufficiency that were studied specifically included atherosis, infarcts, syncytial knots, acute and chronic abruption, hematoma, and fetal thrombosis. The data are shown as median (quartile 1 and quartile 3) or n (%) when appropriate. Results: The anti-angiogenic preeclampsia group ( N = 48) presented at an earlier gestational age (weeks) than the normal angiogenic group ( N = 28); {32 (28, 34) versus 35 (32, 36), p = 0.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus 147 (132, 158), p = 0.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34, 37), p < 0.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus 2655 (2285, 3343), p < 0.001}. Several pathologic lesions were found significantly more often in the anti-angiogenic preeclampsia group; atherosis {27.7% versus 3.6%, p < 0.05}, infarcts {58.3% versus 3.6%, p = 0.002}, and syncytial knots {81.3% versus 39.3%, p < 0.001}. Conclusion: Preeclamptic patients with imbalance in circulating angiogenic factors have disproportionally higher rates of placental vascular lesions historically associated with severe disease. [ABSTRACT FROM AUTHOR]

Glycation of proteins or other biomolecules and their further long-term degradation result in the formation of advanced glycation end products, AGEs. AGEs and other ligands interact with their receptors, RAGEs, localized to a variety of tissues, but mainly in endothelium and vascular wall cells. This interaction triggers diverse signaling pathways that converge on the activation of NF-κB and the initiation of a local inflammatory reaction that, when prolonged, results in dysfunctional features. Preeclampsia is a serious vascular disorder centred at the placenta-uterine interface, the placental bed, but the condition extends to the mother´s circulation. RAGEs have notorious expression in the placental bed tissues along pregnancy but, in addition, RAGEs and their ligands are expressed in the fetal membranes and are found in the amniotic fluid and the mother´s serum. Disorders complicating pregnancies and having an important vascular involvement, as preeclampsia and diabetes mellitus, have additional enhanced AGE/RAGE expression variation. This indicates that for their assessment, the assay of RAGEs or their ligands may become useful diagnostic or prognostic procedures. [ABSTRACT FROM AUTHOR]