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Purpose: New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited. Methods: This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval. Results: 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106 days), and this interval was not significantly different between mild and severe PE (26 days vs. 21 days, P > 0.05) but significantly differed between early-onset and late-onset PE (9 days vs. 28 days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria. Conclusion: New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention to monitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the association of clinical risk factors and placental lesions, in gestations complicated with preeclampsia, with the need for antihypertensive treatment in the early postpartum period. Methods: The computerized files and placental reports of all singleton deliveries at 24.0–42.0 weeks complicated by preeclampsia were reviewed between January 2013 and October 2020. Obstetric characteristics and placental lesions were compared between patients who required antihypertensive treatment in the early postpartum period and those who did not (control group). Placentas were classified into maternal and fetal malperfusion lesions and inflammatory responses. Results: As compared to controls (n = 200), the anti-hypertensive treatment group (n = 95) was characterized by increased rates of preterm birth, preeclampsia with severe features, and cesarean delivery (p < 0.001 for all). More placental hematomas (p = 0.01) and placental maternal vascular lesions (p = 0.03) were observed in the antihypertensive treatment group as compared to controls. In adjusted logistic regression analysis, gestational age (OR 0.86, 95% CI 0.79–0.93, p = 0.001) and preeclampsia with severe features (OR 8.89, 95% CI 3.18–14.93 p < 0.001) were found to be independently associated with the need for postpartum antihypertensive treatment. Conclusion: Placental vascular lesions are more common in preeclamptic patients who need postpartum antihypertensive treatment, yet only early onset of preeclampsia with severe features was found to be independently associated with antihypertensive treatment in the early postpartum period. [ABSTRACT FROM AUTHOR]

Purpose: Obesity and preeclampsia share similar patho-mechanisms and can both affect placental pathology. We aimed to investigate pregnancy outcomes in correlation with placental pathology among pregnancies complicated by preeclampsia in three different maternal body mass index (BMI, kg/m2) groups. Methods: In this retrospective cohort study, medical and pathological records of patients with preeclampsia and a singleton pregnancy delivered between 2008 and 2021 at a single tertiary medical center were reviewed. Study population was divided into three BMI groups: BMI < 22.6 kg/m2 (low BMI group), 22.7 ≤ BMI ≤ 28.0 kg/m2 (middle-range BMI group), and BMI > 28.0 kg/m2 (high BMI group). Data regarding maternal characteristics, neonatal outcomes, and placental histopathological lesions were compared. Results: The study groups included a total of 295 patients diagnosed with preeclampsia—98, 99, and 98 in the low, middle-range, and high BMI groups respectively. Neonatal birth weight was significantly decreased in the low maternal BMI group compared to both middle and high BMI groups (p = 0.04) with a similar trend seen in placental weight (p = 0.03). Villous changes related to maternal malperfusion were more prevalent in the low and high BMI groups compared to middle-range BMI group (p < 0.01) and composite maternal vascular malperfusion lesions were also more prevalent in the groups of BMI extremities compared to the middle-range BMI group (p < 0.01). Conclusion: Maternal BMI might influence neonatal outcomes and placental pathology in pregnancies complicated by preeclampsia. Both extremes of BMI were associated with higher rates of placental maternal vascular malperfusion. Balanced BMI in women at risk for preeclampsia may reduce the incidence of placental lesions. [ABSTRACT FROM AUTHOR]

Background: Pregnant women are also susceptible to SARS-CoV-2. Although an infection of the placenta may be rare, pregnancy may occasionally be affected by intrauterine failure. The knowledge of placental morphology on sudden intrauterine demise is still limited. Methods: Fetal and placental tissue of two cases of sudden intrauterine death in the second trimester were analysed morphologically and by immunohistochemistry. One case was evaluated by RT-PCR. Results: Both mothers were tested positive for the Alpha variant of SARS-CoV-2 but were oligosymptomatic for COVID-19. Unexpected sudden intrauterine death (SIUD) occurred at 15 + 2 and 27 + 3 weeks of gestation. One fetus demonstrated an intrauterine growth restriction. No malformations nor inflammatory changes were observed in either fetus on autopsy. In contrast to the placentas, the fetal tissue was negative for SARS-CoV-2 on immunohistochemical and RT-PCR analyses. Macroscopically, the placentas showed an increased consistency with a white, reticular cutting surface covering about 95% of the whole placenta. Only very focal histiocytic chronic intervillositis was noted histologically. Massive perivillous fibrin deposits with extensive necroses of the villous trophoblast were present in more than 90% of the placental tissue. Immunohistochemical staining was strong and diffusely positive for SARS-CoV-2 in the villous trophoblast and rarely within the villous stromal cells. Placental SARS-CoV-2 infection was confirmed by RT-PCR. Conclusion: Sudden intrauterine death may occur in mothers who are oligosymptomatic for COVID-19. Acute placental failure is responsible for SIUD, demonstrated by massive perivillous fibrin deposits and extensive necroses of the villous trophoblast with SARS-CoV-2-positivity based on immunohistochemical staining and RT-PCR. Detailed histopathological examination of placental and fetal tissue is mandatory to verify SARS-CoV-2 and to evaluate the pathogenesis and functionality of this disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the relationship between maternal left ventricular systolic function, utero-placental circulation, and risk of adverse neonatal outcomes in women with cardiac disease. Methods: 119 women managed in the pregnancy heart clinic (2019–2021) were identified. Women were classified by their primary cardiac condition. Adverse neonatal outcomes were: low birth weight (< 2500 g), small-for-gestational-age (< 10th birth-weight centile), pre-term delivery (< 37 weeks' gestation), and fetal demise (> 20 weeks' gestation). Parameters of left ventricular systolic function (global longitudinal strain, radial strain, ejection fraction, average S', and cardiac output) were calculated and pulsatility index was recorded from last growth scan. Results: Adverse neonatal outcomes occurred in 28 neonates (24%); most frequently in valvular heart disease (n = 8) and cardiomyopathy (n = 7). Small-for-gestational-age neonates were most common in women with cardiomyopathy (p = 0.016). Early pregnancy average S' (p = 0.03), late pregnancy average S' (p = 0.02), and late pregnancy cardiac output (p = 0.008) were significantly lower in women with adverse neonatal outcomes than in those with healthy neonates. There was a significant association between neonatal birth-weight centile and global longitudinal strain (p = 0.04) and cardiac output (p = 0.0002) in late pregnancy. Pulsatility index was highest in women with cardiomyopathy (p = 0.007), and correlated with average S' (p < 0.0001) and global longitudinal strain (p = 0.03) in late pregnancy. Conclusion: Women with cardiac disease may not tolerate cardiovascular adaptations required during pregnancy to support fetal growth. Adverse neonatal outcomes were associated with reduced left ventricular systolic function and higher pulsatility index. The association between impaired systolic function and reduced fetal growth is supported by insufficient utero-placental circulation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness and safety of prophylactic intraoperative uterine artery embolization (UAE) performed immediately after fetal delivery during planned cesarean section or cesarean hysterectomy in patients with placenta accreta spectrum disorder or placenta previa. Methods: A systematic search was conducted on Ovid MEDLINE and Embase, PubMed, Web of Science, and Cochrane databases. Studies were selected using the Population/Intervention/Comparison/Outcomes (PICO) strategy. The intraoperative blood loss and the rate of emergent peripartum hysterectomy (EPH) were the primary outcomes, whereas the length of hospital stay and volume of blood transfused were the secondary outcomes. A random-effects model was employed to pool each effect size. The cumulative values of the primary outcomes were calculated using the generic inverse variance method. Results: Eleven retrospective cohort studies and five case series were included, recruiting 421 women who underwent prophylactic intraoperative UAE (UAE group) and 374 women who did not (control group). Compared with the control group, the UAE group had significantly reduced intraoperative blood loss (p = 0.020) during cesarean section or cesarean hysterectomy. Furthermore, the EPH rate was also significantly decreased (p = 0.020; cumulative rate: 19.65%), but not the length of hospital stay (p = 0.850) and volume of pRBC transfused (p = 0.140), after cesarean section in the UAE group. The incidence of major complications was low (3.33%), despite two patients with uterine necrosis. Conclusion: The currently available data provides encouraging evidence that prophylactic intraoperative UAE may contribute to hemorrhage control and fertility preservation in women with abnormal placentation. Registration: PROSPERO registration code: CRD42021230581. https://clinicaltrials.gov/ct2/show/CRD42021230581 Level of Evidence: Level 2a, systematic review of retrospective cohort studies. [ABSTRACT FROM AUTHOR]

Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors important for its function remain unclear. Renalase is a pro-survival, anti-inflammatory flavoprotein found to be critical in other tissues. We examined the potential role of renalase in placental development. PCR, bulk RNA sequencing, immunohistochemistry, and immunofluorescence for renalase and its binding partners, PMCA4b and PZP, were performed on human placental tissue from second-trimester and full-term placentas separated into decidua, placental villi and chorionic plates. Quantification of immunohistochemistry was used to localize renalase across time course from 17 weeks to term. Endogenous production of renalase was examined in placental tissue and organoids. Renalase and its receptor PMCA4b transcripts and proteins were present in all layers of the placenta. Estimated RNLS protein levels did not change with gestation in the decidual samples. However, placental villi contained more renalase immunoreactive cells in fetal than full-term placental samples. RNLS co-labeled with markers for Hofbauer cells and trophoblasts within the placental villi. Endogenous production of RNLS, PMCA4b, and PZP by trophoblasts was validated in placental organoids. Renalase is endogenously expressed throughout placental tissue and specifically within Hofbauer cells and trophoblasts, suggesting a potential role for renalase in placental development and function. Future studies should assess renalase's role in normal and diseased human placenta. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) and pre-eclampsia with fetal growth restriction (PE/FGR) are high-risk perinatal diseases that may involve high levels of human chorionic gonadotropin (hCG) and mitochondrial dysfunction. However, little is known about how these factors affect placental function. We investigated how mitochondrial dysfunction and high hCG expression affected placental function in unexplained FGR and PE/FGR. We observed elevated expression of hCGβ and growth differentiation factor 15 mRNA and protein levels in the placenta with both diseases. Likewise, antiangiogenic factors, such as Ang2, IP10, sFlt1, IL8, IL1B, and TNFα, were also upregulated at the mRNA level. In addition, the expression of COXI and COXII which encoded by mitochondrial DNA were significantly decreased in both diseases, suggesting that mitochondrial translation was impaired. Treatment with hCG increased Ang2, IP10, IL8, and TNFα mRNA levels in a dose-dependent manner via the p38 and JNK pathways. Mitochondrial translation inhibitors increased hCGβ expression through stabilization of HIF1α, and increased IL8 and TNFα mRNA expression. These results revealed that high expression of hCG due to mitochondrial translational dysfunction plays an important role in the pathogenesis of FGR and PE/FGR. [ABSTRACT FROM AUTHOR]

Purpose: The association between placental detachment disorders and risk of chronic disease is unclear. We determined the association of placenta accreta and retained placenta with risk of future maternal cardiovascular disease and cancer. Methods: We tracked a longitudinal cohort of 541,051 pregnant women over a period of 13 years (2006–2019) in Quebec, Canada. The main exposure measures were placenta accreta and retained placenta in any pregnancy. Outcomes included future hospitalizations for cardiovascular disease and cancer. Using Cox regression models adjusted for maternal characteristics, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of accreta and retained placenta with cardiovascular disease and cancer at 13 years. Results: The incidence of cardiovascular hospitalization was 21.2 per 10,000 person-years for accreta and 23.4 per 10,000 for retained placenta with postpartum hemorrhage, compared with 20.3 per 10,000 for neither placental disorder. Cancer incidence followed a similar pattern, with rates highest for retained placenta with hemorrhage. Retained placenta with hemorrhage was associated with 1.19 times the risk of cardiovascular disease (95% CI 1.03–1.38) and 1.27 times the risk of cancer (95% CI 1.06–1.53). Retained placenta with hemorrhage was associated with heart failure (HR 1.84, 95% CI 1.04–3.27), cardiomyopathy (HR 1.88, 95% CI 1.03–3.43), and cervical cancer (HR 2.03, 95% CI 1.17–3.52). Accreta and retained placenta without hemorrhage were not associated with these outcomes. Conclusion: Retained placenta with hemorrhage may be a risk marker for cardiovascular disease and certain cancers later in life. [ABSTRACT FROM AUTHOR]

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology. [ABSTRACT FROM AUTHOR]

The placenta is the interface between mother and fetus and inadequate function contributes to short and long-term ill-health. The placenta is absent from most large-scale RNA-Seq datasets. We therefore analyze long and small RNAs (~101 and 20 million reads per sample respectively) from 302 human placentas, including 94 cases of preeclampsia (PE) and 56 cases of fetal growth restriction (FGR). The placental transcriptome has the seventh lowest complexity of 50 human tissues: 271 genes account for 50% of all reads. We identify multiple circular RNAs and validate 6 of these by Sanger sequencing across the back-splice junction. Using large-scale mass spectrometry datasets, we find strong evidence of peptides produced by translation of two circular RNAs. We also identify novel piRNAs which are clustered on Chr1 and Chr14. PE and FGR are associated with multiple and overlapping differences in mRNA, lincRNA and circRNA but fewer consistent differences in small RNAs. Of the three protein coding genes differentially expressed in both PE and FGR, one encodes a secreted protein FSTL3 (follistatin-like 3). Elevated serum levels of FSTL3 in pregnant women are predictive of subsequent PE and FGR. To aid visualization of our placenta transcriptome data, we develop a web application (https://www.obgyn.cam.ac.uk/placentome/). Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs. [ABSTRACT FROM AUTHOR]

Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expression deregulations in these diseases, but none has tackled systematically the role of alternative splicing. In the present study, we show that alternative splicing is an essential feature of placental diseases, affecting 1060 and 1409 genes in PE vs controls and IUGR vs controls, respectively, many of those involved in placental function. While in IUGR placentas, alternative splicing affects genes specifically related to pregnancy, in preeclamptic placentas, it impacts a mix of genes related to pregnancy and brain diseases. Also, alternative splicing variations can be detected at the individual level as sharp splicing differences between different placentas. We correlate these variations with genetic variants to define splicing Quantitative Trait Loci (sQTL) in the subset of the 48 genes the most strongly alternatively spliced in placental diseases. We show that alternative splicing is at least partly piloted by genetic variants located either in cis (52 QTL identified) or in trans (52 QTL identified). In particular, we found four chromosomal regions that impact the splicing of genes in the placenta. The present work provides a new vision of placental gene expression regulation that warrants further studies. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth. [ABSTRACT FROM AUTHOR]

Parasites can negatively affect the reproductive success of hosts. Placental species may be particularly susceptible, because parasite-induced stress during pregnancy could potentially influence embryo development. Here, we examine the consequences of a trematode infestation (black spot disease, BSD) for fetal development and adult behavior in 19 natural populations of the placental live-bearing fish species Poeciliopsis retropinna (Poeciliidae) in Costa Rica. First, we observed substantial variation in parasite infestation among populations which correlated with a number of local environmental conditions (elevation, river width, depth, and flow velocity). Furthermore, we observed substantial variation in parasite infestation among females within populations associated with maternal age and size. We found that the infestation rate significantly influenced embryonic development, with more heavily parasitized females producing smaller and worse-conditioned offspring at birth, possibly, because a costly immune response during pregnancy limits, either directly or indirectly, nourishment to developing embryos. Finally, a behavioral experiment in the field showed that the infestation rate did not affect an individual's boldness. Our study indicates that in placental live-bearing fish parasite infestation leads to reduced embryo provisioning during pregnancy, resulting in a smaller offspring size and quality at birth potentially with negative implications for offspring fitness. [ABSTRACT FROM AUTHOR]

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that galectins, an evolutionarily conserved family of glycan-binding proteins, fulfill key roles in pregnancy including blastocyst implantation, maternal-fetal immune tolerance, placental development, and maternal vascular expansion, thereby establishing a healthy environment for the growing fetus. In this review, we comprehensively present the function of galectins in shaping cellular circuits that characterize a healthy pregnancy. We describe the current understanding of galectins in term and preterm labor and discuss how the galectin-glycan circuits contribute to key immunological pathways sustaining maternal tolerance and preventing microbial infections. A deeper understanding of the glycoimmune pathways regulating early events in preterm birth could offer the broader translational potential for the treatment of this devastating syndrome. [ABSTRACT FROM AUTHOR]

Our study aimed to assess perinatal outcomes and recurrence rate of Chronic Intervillositis of Unknown Etiology (CIUE). We conducted an observational retrospective study in a tertiary care university hospital in France from January 1, 1997 to July 31, 2018. 122 pregnancies (102 women) with CIUE were included. Cases of the Department of Histopathology placenta database were re-analysed independently by three pathologists specializing in fetal pathology. Diagnosis of CIUE was confirmed according to: (1) the presence of cellular infiltrate in the intervillous space, (2) ~ 80% of the mononuclear cells in the intervillous space positive for CD68, (3) infiltration occupying at least 5% of the intervillous space, and (4) no clinical or histopathological sign of infection. Outcomes of pregnancies with CIUE (miscarriages, stillbirths, terminations of pregnancy, live birth with or without prematurity or fetal growth restriction) and proportion of CIUE recurrence were analysed. The lost pregnancies comprised 17 (13.9%) miscarriages, 17 (13.9%) stillbirths, and 18 (14.8%) terminations of pregnancy. Of the 70 (57.4%) pregnancies that led to a live birth, 38 (54.3%) new-borns were premature and 50 (72.5%) exhibited fetal growth restriction. Among the 102 women, 23 subsequently became pregnant, half of whom (n = 11) developed recurrent CIUE. CIUE was associated with high rates of adverse perinatal outcomes, including pregnancy loss, fetal growth restriction, and preterm birth with a risk of recurrence nearly 50%. [ABSTRACT FROM AUTHOR]

Objective: To compare the placental elasticity in fetuses with or without intrauterine growth restriction (IUGR).Materials and Methods: One hundred pregnant women (50 IUGR and 50 healthy) with anteriorly located placenta were evaluated during the third trimester of pregnancy. Measurements were carried out by a machine that has a real-time elastographic ultrasonography feature. After obtaining the optimum image, three areas (subcutaneous tissue, center, and the edge of the placenta) were provided to identify the placental strain values. Then, the placental strain ratio (PSR) value was calculated automatically. Two groups compared in terms of their PSR values.Results: There was a significant difference in placental elasticity between the groups (P < 0.001). PSR value was 2.8 ± 1.2 in the IUGR group and 1.3 ± 0.6 in the control group. A PSR value of 1.78 had an 86% sensitivity (OR 4.3) and 80% specificity (OR 0.17) in IUGR cases. The positive predictive value was 81.1% and the negative predictive value was 85.1% for this cut-off value.Conclusions: We have shown that placental strain ratio is increased during the third trimester of pregnancy in fetuses with IUGR. Increased stiffness and elasticity may be responsible for the onset of IUGR in some cases. [ABSTRACT FROM AUTHOR]

Purpose: Pregnancy at advanced maternal age (AMA) has become more common. There has been concern regarding the adverse effect deferring pregnancy might have on pregnancy outcomes. We aimed to prospectively study the effect of AMA on placental pathology.Methods: A prospective case-control study was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of pregnancies with AMA were collected and compared to matched controls. We defined AMA as maternal age > 35 years at delivery. In attempt to isolate the effect of maternal age, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small for gestational age, and congenital/genetic anomalies.Results: The study group included 110 AMA patients that were matched with controls. The groups did not differ in maternal demographics, but the AMA group had a higher rate of assisted reproductive technologies (ART) as compared to the control group (p < 0.001). Placentas in the AMA group were characterized by a higher rate of maternal vascular lesions (MVM) (39.1% vs. 24.5%, p = 0.003), but not fetal vascular malperfusion lesions (p = 0.576). In multivariable analysis maternal age was associated with placental MVM lesions independent of all other maternal demographics (aOR 1.18 95% CI 1.06-3.17). Neonatal outcomes did not significantly differ between the groups.Conclusions: After excluding all background morbidities-AMA was associated with a higher rate of placental MVM lesions vs. controls. These findings suggest an independent effect of AMA on placental function. Large prospective trials are needed to study the clinical importance of these findings. [ABSTRACT FROM AUTHOR]

Objective: In an attempt to shed new light on the pathogenesis of fetal growth restriction (FGR), we aimed to study pregnancy characteristics, neonatal outcomes, and placental histopathological lesions of FGR pregnancies in two different subgroups: when developed after appropriate for gestational age (AGA) pregnancy and when developed after previous pregnancy with FGR.Study Design: Pregnancy and placental reports of all singleton pregnancies complicated by FGR (defined as actual birthweight below the 10th percentile according to local birthweight nomograms) between 2008 and 2018 were reviewed. Included were only cases with previous delivery. Maternal background, neonatal outcomes, and placental histopathology were compared between FGR that occurred after FGR (recurrent FGR group) and FGR that occurred after an AGA pregnancy (FGR after AGA group). Placental lesions were classified according to the current "Amsterdam" criteria. Continuous variables were compared using the Student's t test or the Mann-Whitney test as appropriate. Categorical variables were compared using Chi-square or Fisher's exact test as appropriate.Results: A total of 334 FGR cases with a previous delivery were included in the study. Of them, 111 cases constituted the recurrent FGR group and 223 constituted the FGR after AGA group. The recurrent FGR group was characterized by higher rates of maternal diabetes during pregnancy and hypertensive diseases (9% versus 2.7%, p = 0.01 and 19.8% versus 11.6%, p = 0.04). The FGR after AGA group was characterized by a higher rate of fetal vascular malperfusion (FVM) lesions (29.6% versus 18.0%, p = 0.02), and by lower mean birthweight (1842 ± 424.9 versus 1977.4 ± 412.2, p = 0.005), as compared to the recurrent FGR group.Conclusion: Recurrent FGR was associated with maternal background morbidities during pregnancy which represents a chronic repeated insult, while "new" FGR cases (those followed an AGA pregnancy) were characterized by a higher rate of FVM lesions and lower birthweight which probably represent an "accident" in placentation. These findings may suggest that different mechanisms of placental dysfunction exist in the two subgroups of FGR. [ABSTRACT FROM AUTHOR]

Summary: Introduction Cancers during pregnancy can be treated with chemotherapy after the first trimester but the treatment is associated with smaller placentas and an increased risk of stillbirth, fetal growth retardation and preterm delivery. We decided to assess the effect of several chemotherapeutic agents on placental development by using in vitro culture of human term cytotrophoblasts. Methods Cytotrophoblasts isolated from term placentas were cultured for 48 h and treated for 24 h with epirubicin, docetaxel, vinblastine, methotrexate, tamoxifen, 4-hydroxytamoxifen, and endoxifen. First, cell viability was assessed. Then, the effect of the treatment on trophoblast differentiation and placental angiogenesis was assessed by quantifying hCG and PlGF mRNA and protein expression. Finally, the expression of two efflux transporters, BCRP and MDR1 was investigated. Results Epirubicin only strongly decreased cell viability. Epirubicin, docetaxel, and vinblastine inhibited HCGB and PlGF expression while methotrexate, tamoxifen and its two metabolites increased it. BCRP was essentially expressed in syncytiotrophoblasts and MDR1 in undifferentiated cytotrophoblasts. Their expression was not affected by the drugs but vinblastine increased BCRP mRNA expression by 2.8-fold. Discussion The most commonly used chemotherapeutic drugs are well supported in vitro by syncytiotrophoblasts, except for epirubicin, which was very cytotoxic. Chemotherapy perturbed the expression of genes normally upregulated during placental differentiation and angiogenesis but not the expression of the drug transporters. Further studies looking at the effect of combination therapy and the transporter capacities to reject the drugs will be needed to better define the effects of chemotherapy on placental development and function. [ABSTRACT FROM AUTHOR]

Objectives: This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI.Methods: The published evidence-based data and the opinion of experts were combined using the RAND-UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as "recommended" versus "not recommended" (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts).Results: Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND-UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended.Conclusions: A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI.Key Points: • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as "recommended" for diagnosing PAS disorders. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the rates of retained products of conception (RPOC) after routine postpartum evaluation of patients who underwent post-delivery manual uterine revision due to retained placenta.Methods: This is a retrospective cohort study of 599 consecutive women who underwent manual removal of placenta during 2010-2018. Group A comprised 465 women who underwent postpartum symptom-based evaluation (2010-2016). Group B comprised 134 women who were routinely evaluated by ultrasound and subsequently by hysteroscopic examination 6 weeks after delivery (2016-2018).Results: The rates of abnormal postpartum bleeding were similar between groups A and B (12% and 13%, respectively, p = 0.72%). A significantly smaller proportion of women underwent hysteroscopy in group A than group B (12% vs. 37%, p < 0.05). The rate of persistent RPOC confirmed by hysteroscopy was significantly lower in group A than group B (9.7% vs. 23%, p < 0.05).Conclusion: Among patients who underwent post-delivery manual removal of placenta, a threefold higher rate of RPOC was discovered by routine elective evaluation than by evaluating only symptomatic patients. Future studies may show whether this approach translates to an effect on fertility. [ABSTRACT FROM AUTHOR]

Purpose: Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality, carrying a 20% recurrence rate. The placental disease is a cardinal factor among IUGR underlying processes. This study describes placental histopathological features (HPf) characteristic of recurrent IUGR (rIUGR) and assesses association with antenatal Doppler studies.Methods: We conducted a retrospective case-control study, between the years 2005-2016, evaluating 34 placentae of 17 women with rIUGR, and 59 placentae of a gestational age-matched control. Doppler studies within a week prior to delivery were analyzed for the rIUGR group.Results: Placental HPf characteristic of rIUGR is maternal and fetal vascular malperfusion lesions; maternal accelerated villous maturation and villous infarcts, repetitive feature rate 88.8% (95% CI 37.2-97), and fetal chorionic plate/stem villous thrombi, repetitive feature rate 66.6% (95% CI 30-90.3). Among women with abnormal Doppler, 83.3% had a placenta HPf of maternal vascular malperfusion lesions and 66.7% presented with a hypertensive disorder.Conclusions: Women with rIUGR are a unique group of patients characterized by repetitive placental HPf of both maternal and fetal vascular malperfusion lesions. Specifically, maternal vascular malperfusion lesions are associated with abnormal Doppler findings. In conclusion, characteristic placental HPf may serve as predictors of future IUGR recurrence, thus offering early recognition of pregnancies that require "high-risk" antenatal care. [ABSTRACT FROM AUTHOR]

Purpose: To compare the performance US and MR in identifying placental adhesion spectrum (PAS) in placenta previa (PP) and to establish a potential method of image interpretation. Methods: US and MR examinations of 51 patients with PP were selected. The presence of imaging signs commonly used to detect PAS was assessed. Penalized logistic regression was performed considering histology as standard of reference; only signs statistically significant (p < 0.05) were considered for ROC and multivariate analysis. The probability of PAS according to the presence of US and/or MR signs was then assessed. Results: At univariate analysis, loss of retroplacental clear space, myometrial thinning (MT) and placenta lacunar spaces on US, intraplacental dark bands (IDBs), focal interruption of myometrial border (FIMB) and abnormal vascularity (AV) on MR were statistically significant (p < 0.01). Three diagnostic methods for PAS were then developed for both US and MR when at least one (Method 1), two (Method 2) or three (Method 3) imaging signs occurred, respectively. Method 2 for MR showed a significantly (p < 0.05) higher accuracy (91%) compared to the other methods. When MR IDBs and AV as well as IDBs and FIMB were present in combination with US MT the probability of PAS increased from 75 to 90% and from 80 to 91%, respectively. Conclusion: MR demonstrated a higher diagnostic accuracy than US to detect PAS. However, since the combination of MR and US signs could improve the probability to detect PAS, a complementary diagnostic role of these techniques could be considered. [ABSTRACT FROM AUTHOR]

Objective: To analyze the types of treatment of abnormally invasive placenta (AIP) and to investigate the self-reported physical and mental short- and long-term sequelae.Methods: This single-center observational study was performed between 2003 and 2017. Women with prenatal or intrapartum diagnosis of AIP were identified through the departmental database. Classification was performed according to the time of diagnosis establishment and the type of treatment. Medical complications overall and according to the type of treatment were analyzed. Data about women's perception of diagnosis, treatment, and short- and long-term sequelae were gathered by questionnaire.Results: Cases were classified into four groups: prenatal diagnosis, cesarean hysterectomy (A, n = 10); prenatal diagnosis, expectant management (B, n = 19); intrapartum diagnosis, cesarean hysterectomy (C, n = 6); intrapartum diagnosis, conservative therapy (D, n = 20). Depth of invasion, total units of transfused red blood cells, and the need for reoperation differed between the treatment groups. Expectant management was successful in 94.7% of cases. Irrespective of the treatment group, 73.3% of women perceived the condition as serious or life-threatening; 30.0% utilized psychological support; and 36.7% reported persistent pain or problems. 37.5% of women after uterine preservation had another live birth, AIP recurred in 44.4% of cases.Conclusion: Conservative management of AIP is feasible in selected cases. The condition is perceived as life-threatening and has a lasting impact on the physical, mental, and reproductive health of those affected. This finding merits further investigation. AIP continues to be a condition with high morbidity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the outcomes of uterine-conserving surgery with the occlusion balloon technique followed by uterine or ovarian artery embolization (OAE) in women with placenta accreta.Methods: A total of 31 consecutive patients, who were diagnosed with placenta accreta through grayscale ultrasonography or magnetic resonance imaging prenatally, were retrospectively analyzed in our hospital between October 2015 and September 2017. All of the women underwent a Cesarean section combined with prophylactic placement of a balloon catheter in the abdominal aorta followed by uterine artery embolization (UAE) or OAE when necessary.Results: Technical success was achieved in 31 cases (100%), including successful catheterization and inflation of balloons. The uterus was conserved in 30 (96.77%) patients. The estimated blood loss, packed RBC transfused, and the operation time were 1906.45 ± 1117.64 ml, 4(0-6) U, and 88.68 ± 28.35 min, respectively. Out of all of the patients, we found nine cases of bleeding after the release of the balloon. Among these patients, six cases originated from the ovarian arteries and three cases originated from uterine arteries. Further embolization was performed through catheterization. The mean fetal radiation exposure was 4.33 ± 0.79 mGy.Conclusions: Prophylactic abdominal aorta balloon occlusion followed by UAE or OAE can effectively control postpartum hemorrhaging with reduced blood loss, transfusion requirements, and hysterectomy rates in patients with placenta accreta. [ABSTRACT FROM AUTHOR]

Purpose: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage.Methods: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses.Results: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of a modified type II radical hysterectomy on maternal morbidities and mortality in cases with abnormally invasive placenta (AIP).Methods: 63 cases with AIP were managed at one of the largest referral centers in Egypt in a prospective study design. This technique entails devascularization of the uterus laterally on both sides and to clamp the uterus at the lowest possible point just below the level of the placenta while sparing the ureters.Results: The difference between pre- and post-operative hemoglobin was only about 1 gm/dl, and the mean blood loss was 1673 ± 958 ml. There was a significant drop in the post-operative need for blood and blood product replacement, packed red blood cells (p = 0.013), fresh red blood cells (p < 0.001), and plasma units (p = 0.012). Operative time (skin to skin) averaged 190 ± 58.2 min as the technique is slow and utilizes meticulous hemostatic steps. ICU admission was 4.8% with a mean total hospital stay of 8.6 ± 3.6 days. Histopathological examination revealed 58 cases of placenta increta and five percreta cases. We also had 16 bladder injuries (25.4%) and two ureteric injuries, and no maternal mortalities.Conclusion: This technique reduces maternal morbidity and mortality while performing cesarean hysterectomy for cases with AIP. [ABSTRACT FROM AUTHOR]

Introduction: Hysterectomy is the standard of care in placenta accreta spectrum (PAS). To reduce the risks of obstetric hemorrhage during surgery, endovascular interventions have been proposed. Our aim is to evaluate the feasibility and safety of the overall non-conservative management of PAS in the hybrid operating room (OR) to replace the classic two-step procedure (catheterization in the interventional radiology suite and transfer to conventional OR).Materials and Methods: This is a retrospective study of series of patients with histopathologic confirmation of PAS treated in the hybrid OR at the same university hospital. We used for comparison our historical cohort managed with the standard two-step procedure.Results: We included 110 patients, 80 in the conventional OR and 30 in the hybrid OR. There were no cases of major complications attributable to the endovascular procedures. In the two-step procedure, there were 10 (12.5%) intra-arterial catheter displacements that required repositioning in the conventional OR under mobile C-arm fluoroscopy and no cases in the hybrid OR (p = 0.04). The mean operative time was 380 + 42 min in the conventional OR and 296 + 66 min in the hybrid OR (p = .00001). There were no differences in the gestational age at delivery, postoperative length of stay, or large-volume blood transfusion. There were no maternal deaths.Conclusions: The overall non-conservative management of PAS in the hybrid OR has shown to be feasible and safe in our series, offering potential advantages to replace the classic two-step procedure. More studies are needed to evaluate whether this strategy is cost-effective and whether it may improve maternal and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Background The incidence of severe maternal morbidity (SMM) during childbirth is increasing in the United States. A better characterization of risk factors for SMM may identify targets for improving maternal outcomes. This study aims to characterize patient-, hospital-, and neighborhood-level factors associated with SMM during childbirth. Methods SMM during childbirth was identified in the 2013-2014 State Inpatients Database for New York. Hospital and neighborhood characteristics were abstracted from the American Hospital Association and the Area Health Resources files. Multilevel modeling was used to identify factors associated with SMM, with and without blood transfusion, and its between-hospital variation. Results 403,116 delivery-related discharges from 139 hospitals were analyzed; 1557 (0.39%) recorded SMM without blood transfusion. In the final multilevel model, 7 patient-level factors were associated with a greater than fourfold increase in the risk of SMM: pulmonary hypertension, postpartum hemorrhage, placenta accreta, chronic kidney disease, cardiac conduction disorders, emergent cesarean delivery, and preeclampsia. Three hospital-level factors were associated with SMM: proportion of non-White patients, proportion of Medicaid beneficiaries, and coding intensity. No neighborhood-level factors were predictive of SMM. The proportion of variation in SMM explained by the model was 23.5 with 23.2% related to patient-level factors. The model explained 55% of the between-hospital variation, primarily related to patient-level factors. Similar results were observed for SMM with blood transfusion. Conclusions This study confirms the association between patient-level factors and SMM. It identifies patient-level factors as the major driver of between-hospital variation in SMM. Efforts to improve maternal outcomes should target patient-level factors. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) is the first-line imaging modality to assess the morbidly adherent placenta, but sensitivity and specificity are lacking.Objective: This investigation aims to improve diagnostic accuracy with a comprehensive score using clinical history, US, and magnetic resonance imaging (MRI).Materials and Methods: We conducted a retrospective cohort study of pregnant women who received both transvaginal US and MRI with suspicion for morbidly adherent placenta between 2009 and 2016. US was scored with the following metrics: (i) previa, (ii) hypervascularity, (iii) loss of retroplacental clear space and (iv) lacunae. MRI was evaluated for (i) intraparenchymal vessels, (ii) abnormally dilated vessels, (iii) fibrin deposition, (iv) placental bulge and (v) bladder dome irregularity. Bayesian analysis was used to estimate the probability of morbidly adherent placenta for a given score. Diagnostic testing parameters were calculated.Results: Among the 41 women with concerning imaging, histologically identified disease was confirmed in 16. The probability of morbidly adherent placenta increased with the score. At the highest US score, the probability of disease was 63.7%. With the highest MRI score, the probability of adherent placentation was 90.5%. Combining the US and MRI findings had a sensitivity of 56% and a specificity of 92%.Conclusion: A combined scoring system using MRI and US may accurately identify patients at risk for morbidity associated with morbidly adherent placenta. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of prophylactic balloon occlusion (PBO), and to compare haemostatic effects and perioperative outcomes of PBO of the internal iliac arteries (IIA), common iliac arteries (CIA) and infrarenal abdominal aorta (IAA) in patients with placenta accreta.Methods: One hundred and ninety-nine patients with placenta accreta were retrospectively reviewed. One hundred and twelve cases who underwent PBO were allocated into PBO group, and 87 cases without endovascular intervention were classified as the control group. According to different methods, 112 patients in the PBO group were divided into IIA (n = 37), CIA (n = 42) and IAA (n = 33) subgroups.Results: Patients in the PBO group had decreased estimated blood loss (EBL) and blood transfusion volume (BTV), as well as improved other perioperative outcomes. PBO (vs controls) could independently predict less EBL. As to comparison among subgroups, patients had decreased EBL and BTV, as well as improved other perioperative outcomes in CIA and IAA subgroups compared to the IIA subgroup. Further validation by multivariate analysis revealed that PBO of IIA (vs others) could independently predict more EBL.Conclusions: PBO reduces intraoperative blood loss and improves other perioperative outcomes in patients with placenta accreta, and PBO of the CIA and IAA is more effective compared to PBO of IIA.Key Points: • PBO of IIA, CIA and IAA is effective in placenta accreta. • PBO of CIA and IAA is more effective. • PBO could independently predict less EBL. • Accreta depth was an independent risk factor for EBL. [ABSTRACT FROM AUTHOR]

Objective: To study the role of placental pathology in predicting the recurrence of delivery of small for gestational age (SGA) neonates. Methods: The medical records and placental pathological reports of normotensive women who gave birth at 24 to 42 weeks to neonates with birth weight (BW) <10th percentile were reviewed. Patients were divided according to their subsequent pregnancy into those who developed or did not develop recurrent SGA (BW < 10th percentile). The clinical and pathological characteristics of the index pregnancies were compared between the groups. A prediction model was generated for SGA recurrence. Results: The recurrent SGA group (n = 67) was characterized by a higher rate of placental weight <10th percentile (P = .01), and higher neonatal to placental weight ratio (P = .003), as compared to the nonrecurrent SGA group (n = 99). On multivariate logistic regression analysis, placental maternal and fetal vascular malperfusion lesions and higher neonatal to placental weight ratio were all independently associated with recurrent SGA. Birth weight <3rd percentile was the only clinical variable associated with recurrent SGA. A prediction model for recurrent SGA included the following independent risk factors: BW <3rd percentile, villous lesions of maternal vascular malperfusion, and neonatal to placental weight ratio. Conclusion: The presence of placental vascular malperfusion lesions and increased neonatal to placental weight ratio at index pregnancy are associated with recurrent SGA in subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: To report on outcomes following the use of prophylactic internal iliac artery occlusion balloons in patients with abnormal placental implantation.Methods: A retrospective analysis was undertaken of patients with abnormal placental implantation who underwent prophylactic iliac balloon placement prior to delivery in a University Maternity Hospital. Various clinical and technical factors were analysed, including technical success of balloon placement, blood loss and number of blood units transfused, duration of surgery, length of stay, hysterectomy rates, complications related to the balloon insertion, foetal pH and infant Apgar scores.Results: Twenty-two patients with placenta accreta or a variant thereof underwent caesarean section after first undergoing prophylactic placement of bilateral internal artery balloons. Average follow-up duration was 2.08 years. The average gestational age was 37 weeks 6 days, and the mean gravidity was 2.8. The mean number of previous caesarean sections was 2.4, while the mean maternal age was 35 years. The mean intraoperative blood loss was 1.4 L, and the mean number of blood units transfused was 2. Mean duration of surgery was 90 min, mean total length of hospital stay 7.5 days, while the mean duration of ICU/HDU stay was 1.2 days. The balloons were inflated in 60% of cases and two patients (2/22-9%) underwent subsequent hysterectomy. There were no major maternal complications due to the procedure.Conclusion: Prophylactic placement of arterial balloons prior to caesarean section in patients with placenta accreta is well tolerated and leads to satisfactory maternal and foetal outcomes with minimal complications. [ABSTRACT FROM AUTHOR]

Purpose: In our study, we try to investigate whether magnesium sulphate (MgSO4) could provide protection against oxidative damage and inflammatory response in rat placenta of intrahepatic cholestasis of pregnancy (ICP) model.Methods: The rat model of ICP was established by injecting s.c. 17α-ethinyl estradiol (EE) daily for 5 days. MgSO4, as an therapeutic drug for ICP, was injected i.p. daily for 3 days. Age-matched pregnant rats served as controls. The level of serum total bile acid (TBA) was measured. The data including the number and weight of offsprings on day 20 of pregnancy were collected. We observed ultrastructural changes of mitochondria and endoplasmic reticulum (ER) in placenta by transmission electron microscope. The antioxidant proteins peroxiredoxin-6 (Prdx6) and nuclear factor erythroid 2-related factor-2 (Nrf2) were analyzed by Western Blot. The inflammatory cytokines including IL-1β, TNF-α and IFN-γ were investigated by real-time PCR (RT-PCR) and enzyme-linked immune-sorbent assay (ELISA).Results: The weight of offsprings on day 20 of pregnancy increased in ICP rats treated with MgSO4 (ICP + MG group) compared with that in ICP rats (ICP group). However, the level of TBA was not reduced. The damage of mitochondria and ER was observed in placenta, which was much more slighter in ICP + MgSO4 group as compared with that in ICP group. Prdx6 and Nrf2 were increased, while the inflammatory cytokines including IL-1β, TNF-α and IFN-γ were decreased in ICP + MgSO4 group compared with that in ICP group.Conclusions: MgSO4 had beneficial effect on improving growth of offsprings in rat model of ICP. The protective effect of MgSO4 on alleviating oxidative damage and inflammatory response in placenta may play an important role in the process. MgSO4 may improve the function of placenta. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the imaging characteristics and accuracy of T2-weighted (T2W) balanced steady-state free procession (b-SSFP) magnetic resonance imaging, relative to b-SSFP or single-shot fast spin echo (SSFSE), for the diagnosis of placental adhesion disorder (PAD).Methods: Fifty-one pregnant patients suspected of PAD were examined with T2W b-SSFP, b-SSFP and SSFSE. The image types were independently analysed for signs of PAD: abnormal placental bulge (APB), dark intraplacental bands (DIB), placental heterogeneity (PH) and placental protrusion into adjacent structures (PPAS). The sequences were compared for muscle-to-placenta signal ratio, signs of PAD and area under the receiver operating characteristic curve (AUC) for diagnostic accuracy of PAD.Results: PAD was confirmed in 34 women. The muscle-to-placenta signal ratio was highest in the T2W b-SSFP. The diagnostic rates of APB in T2W b-SSFP were comparable to that of b-SSFP, but were significantly higher than that of SSFSE. The rates of PH in SSFE were comparable to that of b-SSFP, but both were significantly lower than that of T2W b-SSFP. The rates of DIB were significantly higher in T2W b-SSFP images compared with SSFSE. Rates of PPAS were comparable among three sequences. The AUCs of the T2W b-SSFP, b-SSFP and SSFSE were 0.966, 0.890 and 0.823, respectively.Conclusion: T2W b-SSFP has high diagnostic accuracy for PAD relative to SSFSE or b-SSFP, which may be due to its high SNR, T2-weighting and lack of blur.Key Points: • Signal myometrium-to-placenta ratio was highest in the T2W b-SSFP images. • Diagnostic rate of APB in T2W b-SSFP was highest. • Diagnostic rate of DIB was higher in T2W b-SSFP than in SSFSE. • Diagnostic rate of PH in T2W b-SSFP was highest. • Maximum AUC for diagnostic accuracy of PAD was in T2W b-SSFP. [ABSTRACT FROM AUTHOR]

Objective: Placenta percreta (PP) is an abnormal condition of trophoblast maturation and terminal differentiation through the uterine wall. We opted to study telomere homeostasis and senescence expression in trophoblasts from PP, the most severe subgroup of placenta accreta. Study Design: Paraffin-embedded placental biopsies from pregnancies with percreta and normal placentation, matched by gestational age at delivery, were assessed for telomere length, aggregates, and senescence-associated heterochromatin foci using quantitative fluorescence in situ hybridization. Cyclin-dependent kinase inhibitors p21, p15, p16, and the tumor suppressor protein p53, known senescence-related markers, were assessed using immunohistochemical staining. Results: Short telomeres were found more often in trophoblasts from the samples of PP (n = 9) compared to controls (n = 8; 54% ± 20% vs 2.3% ± 1.16%, respectively; P < .05). More cells with telomere aggregates (18.3% ± 6.9%) were observed in the PP than in the control group (4.8% ± 5.4%; P = .0005). The percentage of nucleic senescence-associated heterochromatin foci in the PP and control samples was similar (10.9% ± 10.4% vs 10.7% ± 15%, respectively; P = .97). Immunohistochemistry of senescence markers was expressed differently in PP compared to the controls: higher p15 expression (46.42% ± 15.2% vs 36.63% ± 12.2%, P = .004), higher p21 expression (59.8% ± 22.1% vs 47.5% ± 21.9%, P = .011), lower p16 expression (54.8% ± 26.3% vs 73.4% ± 18.9%, P = .000), and lower p53 expression (24.4% ± 33.8% vs 34% ± 14.4%, P = .000). Conclusion: Placenta percreta exhibits telomere alterations and changes in expression of several senescence markers. These might be related to altered trophoblast invasion maturation and placental detachment postpartum. [ABSTRACT FROM AUTHOR]

Purpose: Prophylactic placement of endovascular balloon occlusion catheters has grown to be part of the surgical plans to control intraoperative hemorrhage in cases of abnormal placentation. We performed a systematic literature review to investigate the safety and effectiveness of the use of REBOA during cesarean delivery in pregnant woman with morbidly adherent placenta.Methods: A systematic review was performed. Relevant case reports and nonrandomized studies were identified by the literature search in MEDLINE. We included studies involving pregnant woman with diagnosis of abnormal placentation who underwent cesarean delivery with REBOA placed for hemorrhage control. MINORS’ criteria were used to evaluate the risk of bias of included studies. A formal meta-analysis was not performed.Results: Eight studies were included in cumulative results. These studies included a total of 392 patients. Overall, REBOA was deployed in 336 patients. Six studies reported the use of REBOA as an adjunct for prophylactic hemorrhage control in pregnant woman with diagnosis of morbidly adherent placenta undergoing elective cesarean delivery. In two studies, REBOA was deployed in patients already in established hemorrhagic shock at the moment of cesarean delivery. REBOA was deployed primarily by interventional radiologists; however, one study reported a surgeon as the REBOA provider. The results from our qualitative synthesis indicate that the use of REBOA during cesarean delivery resulted in less blood loss with a low rate complications occurrence.Conclusion: REBOA is a feasible, safe, and effective means of prophylactic and remedial hemorrhage control in pregnant women with abnormal placentation undergoing cesarean delivery. [ABSTRACT FROM AUTHOR]

Objective: We aimed to compare the differences in placental histopathology lesions and pregnancy outcome in dichorionic–diamniotic (DCDA) versus uncomplicated monochorionic–diamniotic (MCDA) twin gestations. Study Design: Maternal characteristics, neonatal outcome, and placental histopathology reports of all twin deliveries between 24 and 41 weeks were reviewed. Excluded were pregnancies complicated by twin-to-twin transfusion syndrome, twin anemia–polycythemia sequence, selective intrauterine growth restriction, placenta previa, intrauterine fetal death, and malformation. Placental lesions were classified to maternal/fetal vascular malperfusion lesions. Umbilical cord abnormalities included hypo-/hypercoiling and abnormal insertion. Composite adverse neonatal outcome was defined as 1 or more early complications. Small for gestational age (SGA) was defined as birth weight ≤10th percentile. Results: The DCDA group (n = 362) was characterized by higher rates of assisted reproductive techniques (P < .001) and nulliparity (P = .03) as compared to the MCDA group (n = 65). Gestational age at delivery was similar between groups. Placental maternal vascular malperfusion lesions were more common in placentas from DCDA group (38.2% vs 23.1%; P = .016), while fetal vascular malperfusion lesions and abnormal cord insertion were more common in placentas from MCDA group (P = .027; P< .001). The SGA and composite adverse neonatal outcome were more common in the MCDA group (P = .031 and P = .038, respectively). By multivariate regression analysis, composite adverse neonatal outcome was found to be independently associated with the MCDA group, adjusted odds ratio (aOR) = 1.2, 95% confidence interval (CI) = 1.04 to 1.89, P = .041, and with placental fetal malperfusion lesions aOR = 1.3, 95% CI = 1.1 to 2.09, P = .038. Conclusion: Placental pathology differs between MCDA and DCDA twin pregnancies. Adverse neonatal outcome in uncomplicated MCDA twins, as compared to DCDA twins, could be related to increased placental fetal malperfusion lesions and abnormal cord insertion. [ABSTRACT FROM AUTHOR]

Objective: To (a) evaluate the risk for placenta accreta following primary cesarean section (CS), in regard to the stage of labor, the cesarean section was taken (elective prelabor vs. unplanned during labor); and (b) investigate whether the association between placenta accreta and maternal and neonatal complications is modified by the type of the primary CS.Study Design: In a population-based retrospective cohort study, we included all singleton deliveries occurred in Soroka University Medical Center between 1991 and 2015, of women who had a history of a single CS. The deliveries were divided into three groups according to the delivery stage the primary CS was carried out: 'Unplanned 1' (first stage-up to 10 cm), 'Unplanned 2' (second stage-10 cm) and 'Elective' prelabor CS. We assessed the association between the study group and placenta accreta using logistic generalized estimation equation (GEE) models. We additionally assessed maternal and neonatal complications associated with placenta accreta among women who had elective and unplanned CS separately.Results: We included 22,036 deliveries to 13,727 women with a history of one CS, of which 0.9% (n = 207) had placenta accreta in the following pregnancies: 12% (n = 25) in the 'Unplanned 1' group, 7.2% (n = 15) in the ' Unplanned 2' group and 80.8% (n = 167) in the 'elective' group. We found no difference in the risk for subsequent placenta accreta between the groups. In a stratified analysis by the timing of the primary cesarean delivery, the risk for maternal complications, associated with placenta accreta, was more pronounced among women who had an unplanned CS (OR 27.96, P < 0.01) compared to women who had an elective cesarean delivery (OR 13.72, P < 0.01).Conclusions: The stage in which CS is performed has no influence on the risk for placenta accreta in the following pregnancies, women who had an unplanned CS are in a higher risk for placenta accrete-associated maternal complications. This should be taken into consideration while counselling women about their risk while considering trial of labor after cesarean section. [ABSTRACT FROM AUTHOR]

Purpose: A retained placenta after vaginal delivery where manual removal of placenta fails is a clinical challenge. We present six cases that illustrate the heterogeneity of the condition and discuss the etiology and terminology as well as the clinical management.Methods: Members of the European Working group on Abnormally Invasive Placenta (EW-AIP) were invited to report all recent cases of retained placenta that were not antenatally suspected to be abnormally adherent or invasive, but could not be removed manually despite several attempts.Results: The six cases from Denmark, The Netherlands and the UK provide examples of various treatment strategies such as ultrasound-guided vaginal removal, removal of the placenta through a hysterotomy and just leaving the placenta in situ. The placentas were all retained, but it was only possible to diagnose abnormal invasion in the one case, which had a histopathological diagnosis of increta. Based on these cases we present a flow chart to aid clinical management for future cases.Conclusion: We need properly defined stringent terminology for the different types of retained placenta, as well as improved tools to predict and diagnose both abnormally invasive and abnormally adherent placenta. Clinicians need to be aware of the options available to them when confronted by the rare case of a retained placenta that cannot be removed manually in a hemodynamically stable patient. [ABSTRACT FROM AUTHOR]

Objective: To report our experience on the value of transcatheter arterial embolization (TAE) or transcatheter arterial chemoembolization (TACE) for the uterus-preserving management of retained placenta accreta with marked vascularity after abortion or delivery.Study Design: Thirty-eight consecutive women with retained placenta accreta were retrospectively analyzed over a 5-year period. When elevated levels of serum β-hCG (> 25 mIU/mL) were detected, TACE with dactinomycin was chosen for devascularization along with cytotoxic effects on active trophoblasts; in contrast, if the serum β-hCG level was low (≤ 25 mIU/mL), TAE was chosen. After confirming devascularization, the additional need for hysteroscopic resection and systemic methotrexate administration was individually determined.Results: The most frequent sign and symptom in the abortion group was significant hemorrhaging, while a hypervascular mass detected at a regular check-up was the most frequent in the delivery group. The median time elapsed between abortion and endovascular management was 36 days, and the median time elapsed after delivery was 31.5 days. TACE was performed more frequently than TAE in the abortion group, while TAE was the more frequent procedure in the delivery group. In 10 and 11 cases, after abortion and delivery, respectively, hysteroscopic resection was performed. Systemic methotrexate administration was additionally done in three and one cases after abortion and delivery, respectively. Uterine preservation was achieved in all cases.Conclusion: This case series emphasizes that endovascular embolization is an effective key intervention with or without additional therapies for uterus-preserving management of retained placenta accreta with marked vascularity after abortion or delivery. [ABSTRACT FROM AUTHOR]

Aim: To describe a modified "Triple-P" procedure and evaluate its outcome in women with morbidly adherent placenta (MAP) after previous caesarean section (CS).Methods: A retrospective cohort study of 96 women with MAP after CS was recruited with 45 women receiving the modified "Triple-P" procedure as study group and the other 51 cases receiving the conventional managements as the control. The maternal outcomes were compared.Results: The modified "Triple-P" procedure was described in step by step. Women in study group demonstrated reduction of blood loss, transfusion blood volume and operation time, as well as less hospital days and lower hospitalization cost (P < 0.05). In addition, there was no difference in uterine healing rate, hysterectomy rate, and ICU transferring rate (P > 0.05).Conclusion: Our modified "Triple-P" procedure for MAP after previous CS maintained the advantages of Chandraharan's "Triple-P" procedure in preservation of uterus for further fertility, less intraoperative blood loss, shorter hospital stays, and lower hospitalization cost but also advanced in feasibility and convenience during introducing into routine clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to prenatally predict placenta accreta in posterior placenta previa using magnetic resonance imaging (MRI).Methods: This retrospective study was approved by the Institutional Review Board of our hospital. We identified 81 patients with singleton pregnancy who had undergone cesarean section due to posterior placenta previa at our hospital between January 2012 and December 2016. We calculated the sensitivity and specificity of several well-known findings, and of cervical varicosities quantified using magnetic resonance imaging, in predicting placenta accreta in posterior placenta previa. To quantify cervical varicosities, we calculated the A/B ratio, where "A" was the minimum distance from the most dorsal cervical varicosity to the deciduous placenta, and "B" was the minimum distance from the most dorsal cervical varicosity to the amniotic placenta. The appropriate cut-off value of the A/B ratio was determined using a receiver operating characteristic (ROC) curve.Results: Three patients (3.7%) were diagnosed as having placenta accreta. The sensitivity and specificity of the well-known findings were 0 and 97.4%, respectively. Furthermore, the A/B ratio ranged from 0.02 to 0.79. ROC curve analysis revealed that the area under the combined placenta accreta and A/B ratio curve was 0.96. When the cutoff value of the A/B ratio was set 0.18, the sensitivity and specificity were 100 and 91%, respectively.Conclusion: It was difficult to diagnose placenta accreta in the posterior placenta previa using the well-known findings. The quantification of cervical varicosities could effectively predict placenta accreta. [ABSTRACT FROM AUTHOR]

Purpose: To confirm reduced expression of soluble fms-like tyrosine kinase 1 (sFlt-1) in accreta/increta.Methods: Formalin-fixed tissue sections from 11 peripartum hysterectomies with invasive placentation and 5 controls were stained for sFlt-1. Stain intensity was scored in selected 100× microscopic fields. We compared sFlt-1 expression in invasive areas among cases, non-invasive areas among cases and areas from control placentas.Results: Chorionic villi displayed significantly decreased sFlt-1 expression in invasive areas of cases compared to control placentas (p = 0.003), as well as in non-invasive areas of cases compared to control placentas (p = 0.01). There was no difference in sFlt-1 expression between invasive and non-invasive areas among cases.Conclusions: Expression of sFlt-1 is diminished in villous trophoblasts from patients with placenta increta or percreta. Local depth of invasion was not associated with sFlt-1 expression, suggesting a more global abnormality across the implantation site rather than localized to areas of histologic invasion. [ABSTRACT FROM AUTHOR]

Purpose: It is important to predict massive postpartum hemorrhage in patients with placenta previa totalis (PPT) and a method that accurately predicts this event is needed. The present study developed a scoring system that predicts massive transfusion in patients with PPT. Methods: This single-center retrospective cohort study comprised 238 patients with PPT who underwent caesarean section between January 2004 and December 2010. Massive transfusion was defined as the transfusion of ≥8 units of packed red blood cells within 24 h after delivery. Multivariate regression analysis was used to estimate the risks of massive transfusion. A probability score model was then constructed and tested for performance. Subsequently, the model was validated in other patients with PPT ( n = 117). Results: Thirty-one patients (13.0%) underwent massive transfusion. Ultrasound suspicion of placental adhesion, previous caesarean section, gestational age <37 weeks, sponge-like appearance of the cervix, and anterior placenta were all independent predictors of massive transfusion. The performance for the score model revealed good calibration (Hosmer-Lemeshow chi-squared 1.64; P = 0.44), and its discrimination (the area under the receiver operating characteristic for this model was 0.84) was better than when suspicion of placental adhesion was used alone (0.67; P < 0.001). In the validation set, the performance was 0.88. Conclusion: The scoring system developed using the five independent risk factors had better performance to predict massive transfusion in patients with PPT than when suspicion of placental adhesion was used alone. However, further large-scale studies are warranted to clarify the usefulness and accuracy of this model. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) (gestational proteinuric hypertension) is the leading cause of maternal and perinatal mortality worldwide. Although placental endothelial dysfunction and oxidative stress are known to contribute to PE, the exact pathological basis for this disorder remains unclear. Previously, we demonstrated that DNA damage at the maternal–fetal interface is more common in the placentas of women with PE than normotensive controls. In this study, we utilized an in vivo comparative study, including 20 preeclamptic women and 8 healthy control subjects, and an in vitro hypoxia/reperfusion model to mimic the effects of oxidative stress at the maternal–fetal interface. We tracked the spatial pattern of expression of 2 base excision repair proteins, 8-oxoguanine glycosylase (OGG1) and apurinic/apyrimidinic endonuclease-1 (APE1), at the maternal–fetal interface in response to oxidative stress. In vivo, we found a significant increase in OGG1 and APE1 concentrations in PE placental tissues as compared to normotensive controls (P < .0001). Further, our in vitro study revealed that OGG1 and APE1 expression is much greater in maternal cells (decidua) than in fetal cells (cytotrophoblasts) of placental tissue subjected to oxidative stress (P < .0001). Our results suggest that OGG1 and APE1 likely protect decidual cells from oxidative base damage. [ABSTRACT FROM AUTHOR]

Objectives: Arterial embolisation (AE) plays a major role in current practice in the management of postpartum haemorrhage (PPH) that fails to respond to conservative treatment. While its benefit is well known, long-term outcomes of AE have been poorly investigated. The objective of this review is to assess its potential complications and long-term effects on the patients' quality of life.Methods: Using the terms "embolisation" and "postpartum haemorrhage", we searched the Cochrane Central Register of Controlled Trials, Medline and PubMed for published studies. We limited the search to articles in English and French reporting "complications", "fertility", "menstruation" or "menstrual cycle" in humans. To ensure completeness, the references of extracted articles and review articles were also searched.Results: The fertility rate in patients attempting another pregnancy reaches 70-80 %. Pregnancies following AE for PPH are not associated with a higher rate of intrauterine growth restriction. Pathological placentation (placenta accreta/increta/percreta) occurs more frequently after AE than in the general population. Psychological wellbeing, post-traumatic stress and sexual dysfunction after a life-threatening PPH requiring AE will require further investigation.Conclusion: AE does not appear to adversely affect menstrual cycle, fertility and subsequent pregnancies, but may affect placentation. The experience of a life-threatening PPH, however, might prevent couples from pursuing another pregnancy.Key Points: • Embolisation for PPH does not adversely affect menstrual cycle and fertility • Experience of life-threatening PPH might prevent couples from pursuing another pregnancy • Pathological placentation seems to occur more frequently after embolisation for PPH. [ABSTRACT FROM AUTHOR]