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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]

Placenta accreta spectrum (PAS) is a relatively new obstetric condition which, until recently, was poorly understood. The true incidence is unknown because of the poor quality and heterogeneous diagnostic criteria. Classification systems have attempted to provide clarity on how to grade and diagnose PAS, but these are no longer reflective of our current understanding of PAS. This is particularly true for placenta percreta, which referred to extrauterine disease, as recent studies have demonstrated that placental villi associated with PAS have minimal potential to invade beyond the uterine serosa. It is accepted that PAS is a direct consequence of previous iatrogenic uterine injury, most commonly a previous cesarean section. Here, we “look back to look forwards”—starting with the primary predisposing factor for PAS, an iatrogenic uterine injury and subsequent wound healing. We then consider the evolution of definitions and diagnostic criteria of PAS from its first description over a century ago to current classifications. Finally, we discuss why modifications to the current classifications are needed to allow accurate diagnosis of this rare but life‐threatening complication, while avoiding overdiagnosis and potential patient harm. [ABSTRACT FROM AUTHOR]

Background: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD‐10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life‐threatening pregnancy complication that is increasing in incidence. Objective: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD‐10 and assess contributing factors to incorrect code assignments. Methods: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD‐10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard. Results: Among 22,345 patients, 104 (0.46%) had an ICD‐10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD‐10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD‐10 codes for placenta accreta spectrum subtypes— accreta, increta and percreta—were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features. Conclusion: These findings from a quaternary obstetric centre suggest that ICD‐10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases. [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]

Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF‐1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast‐specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short‐ and long‐term consequences of abnormal fetal growth in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND The placenta is a unique and pivotal organ in reproduction, controlling crucial growth and cell differentiation processes that ensure a successful pregnancy. Placental development is a tightly regulated and dynamic process, in which the transforming growth factor beta (TGFβ) superfamily plays a central role. This family of pleiotropic growth factors is heavily involved in regulating various aspects of reproductive biology, particularly in trophoblast differentiation during the first trimester of pregnancy. TGFβ signalling precisely regulates trophoblast invasion and the cell transition from cytotrophoblasts to extravillous trophoblasts, which is an epithelial-to-mesenchymal transition-like process. Later in pregnancy, TGFβ signalling ensures proper vascularization and angiogenesis in placental endothelial cells. Beyond its role in trophoblasts and endothelial cells, TGFβ signalling contributes to the polarization and function of placental and decidual macrophages by promoting maternal tolerance of the semi-allogeneic foetus. Disturbances in early placental development have been associated with several pregnancy complications, including preeclampsia (PE) which is one of the severe complications. Emerging evidence suggests that TGFβ is involved in the pathogenesis of PE, thereby offering a potential target for intervention in the human placenta. OBJECTIVE AND RATIONALE This comprehensive review aims to explore and elucidate the roles of the major members of the TGFβ superfamily, including TGFβs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, and growth differentiation factors (GDFs), in the context of placental development and function. The review focusses on their interactions within the major cell types of the placenta, namely trophoblasts, endothelial cells, and immune cells, in both normal pregnancies and pregnancies complicated by PE throughout pregnancy. SEARCH METHODS A literature search was carried out using PubMed and Google Scholar, searching terms: 'TGF signalling preeclampsia', 'pregnancy TGF signalling', 'preeclampsia tgfβ', 'preeclampsia bmp', 'preeclampsia gdf', 'preeclampsia activin', 'endoglin preeclampsia', 'endoglin pregnancy', 'tgfβ signalling pregnancy', 'bmp signalling pregnancy', 'gdf signalling pregnancy', 'activin signalling pregnancy', 'Hofbauer cell tgfβ signalling', 'placental macrophages tgfβ', 'endothelial cells tgfβ', 'endothelium tgfβ signalling', 'trophoblast invasion tgfβ signalling', 'trophoblast invasion Smad', 'trophoblast invasion bmp', 'trophoblast invasion tgfβ', 'tgfβ preeclampsia', 'tgfβ placental development', 'TGFβ placental function', 'endothelial dysfunction preeclampsia tgfβ signalling', 'vascular remodelling placenta TGFβ', 'inflammation pregnancy tgfβ', 'immune response pregnancy tgfβ', 'immune tolerance pregnancy tgfβ', 'TGFβ pregnancy NK cells', 'bmp pregnancy NK cells', 'bmp pregnancy tregs', 'tgfβ pregnancy tregs', 'TGFβ placenta NK cells', 'TGFβ placenta tregs', 'NK cells preeclampsia', 'Tregs preeclampsia'. Only articles published in English until 2023 were used. OUTCOMES A comprehensive understanding of TGFβ signalling and its role in regulating interconnected cell functions of the main placental cell types provides valuable insights into the processes essential for successful placental development and growth of the foetus during pregnancy. By orchestrating trophoblast invasion, vascularization, immune tolerance, and tissue remodelling, TGFβ ligands contribute to the proper functioning of a healthy maternal–foetal interface. However, dysregulation of TGFβ signalling has been implicated in the pathogenesis of PE, where the shallow trophoblast invasion, defective vascular remodelling, decreased uteroplacental perfusion, and endothelial cell and immune dysfunction observed in PE, are all affected by an altered TGFβ signalling. WIDER IMPLICATIONS The dysregulation of TGFβ signalling in PE has important implications for research and clinical practice. Further investigation is required to understand the underlying mechanisms, including the role of different ligands and their regulation under pathophysiological conditions, in order to discover new therapeutic targets. Distinguishing between clinically manifested subtypes of PE and studying TGFβ signalling in different placental cell types holistically is an important first step. To put this knowledge into practice, pre-clinical animal models combined with new technologies are needed. This may also lead to improved human research models and identify potential therapeutic targets, ultimately improving outcomes for affected pregnancies and reducing the burden of PE. [ABSTRACT FROM AUTHOR]

BACKGROUND With increasing significance of developmental programming effects associated with placental dysfunction, more investigations are devoted to improving the characterization and understanding of placental signatures in health and disease. The placenta is a transitory but dynamic organ adapting to the shifting demands of fetal development and available resources of the maternal supply throughout pregnancy. Trophoblasts (cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts) are placental-specific cell types responsible for the main placental exchanges and adaptations. Transcriptomic studies with single-cell resolution have led to advances in understanding the placenta's role in health and disease. These studies, however, often show discrepancies in characterization of the different placental cell types. OBJECTIVE AND RATIONALE We aim to review the knowledge regarding placental structure and function gained from the use of single-cell RNA sequencing (scRNAseq), followed by comparing cell-type-specific genes, highlighting their similarities and differences. Moreover, we intend to identify consensus marker genes for the various trophoblast cell types across studies. Finally, we will discuss the contributions and potential applications of scRNAseq in studying pregnancy-related diseases. SEARCH METHODS We conducted a comprehensive systematic literature review to identify different cell types and their functions at the human maternal–fetal interface, focusing on all original scRNAseq studies on placentas published before March 2023 and published reviews (total of 28 studies identified) using PubMed search. Our approach involved curating cell types and subtypes that had previously been defined using scRNAseq and comparing the genes used as markers or identified as potential new markers. Next, we reanalyzed expression matrices from the six available scRNAseq raw datasets with cell annotations (four from first trimester and two at term), using Wilcoxon rank-sum tests to compare gene expression among studies and annotate trophoblast cell markers in both first trimester and term placentas. Furthermore, we integrated scRNAseq raw data available from 18 healthy first trimester and nine term placentas, and performed clustering and differential gene expression analysis. We further compared markers obtained with the analysis of annotated and raw datasets with the literature to obtain a common signature gene list for major placental cell types. OUTCOMES Variations in the sampling site, gestational age, fetal sex, and subsequent sequencing and analysis methods were observed between the studies. Although their proportions varied, the three trophoblast types were consistently identified across all scRNAseq studies, unlike other non-trophoblast cell types. Notably, no marker genes were shared by all studies for any of the investigated cell types. Moreover, most of the newly defined markers in one study were not observed in other studies. These discrepancies were confirmed by our analysis on trophoblast cell types, where hundreds of potential marker genes were identified in each study but with little overlap across studies. From 35 461 and 23 378 cells of high quality in the first trimester and term placentas, respectively, we obtained major placental cell types, including perivascular cells that previously had not been identified in the first trimester. Importantly, our meta-analysis provides marker genes for major placental cell types based on our extensive curation. WIDER IMPLICATIONS This review and meta-analysis emphasizes the need for establishing a consensus for annotating placental cell types from scRNAseq data. The marker genes identified here can be deployed for defining human placental cell types, thereby facilitating and improving the reproducibility of trophoblast cell annotation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Preeclampsia has been linked to an inflammatory response that may be brought on by endothelial cell dysfunction. This paper investigates the pathomechanism of syncytiotrophoblast basement membrane (STBM) damage and Placental Protein 13 (PP13) release, which may have a role in systemic endothelial dysfunction in preeclampsia. Materials and Methods: This comparative cross-sectional study involves 54 preeclampsia patients (27 early-onset preeclampsia and 27 late-onset preeclampsia) and 27 pregnant women with normal blood pressure. An enzyme-linked immunosorbent assay was performed to evaluate maternal blood levels of PP13. Following birth, a portion of the placenta was collected for transmission electron microscope (TEM) and immunohistochemical (IHC) analysis. The data were analyzed using STATA version 15. Results: PP13 expression in the placental syncytiotrophoblast was significantly lower in the early-onset preeclampsia, compared to late-onset preeclampsia and normotensive pregnancy, group (p < 0.001). In contrast, serum PP13 levels were found to be the highest in the early-onset preeclampsia group, although no significant difference were found in mean maternal serum levels of PP13 between the three groups. The decreased PP13 expression in placental syncytiotrophoblast can be attributed to the greater extent of damage in the STBM in early-onset preeclampsia that leads to the release of a larger amount of PP13 into maternal circulation. The hypothesis aligns with the TEM analysis results. Preeclamptic pregnancies showed placental syncytiotrophoblast aponeurosis, whereas normotensive pregnancies did not. Placental lesions and STBM shedding were found to be more pronounced in early-onset preeclampsia compared to late-onset preeclampsia. Conclusions: PP13 and STBM damage may play a role in systemic endothelial dysfunction in preeclampsia. [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]

Problem: Early‐onset preeclampsia (EOPE) is a severe gestational hypertensive disorder with significant feto‐maternal morbidity and mortality due to uteroplacental insufficiency. Circulating extracellular vesicles of placental origin (EV‐P) are known to be involved in the pathophysiology of EOPE and might serve as an ideal reservoir for its specific biomarkers. Therefore, we aimed to characterize and perform comparative proteomics of circulating EV‐P from healthy pregnant and EOPE women before delivery. Method of Study: The EV‐P from both groups were isolated using immunoaffinity and were characterized using transmission electron microscopy, dynamic light scattering, nanoparticle tracking analysis, and immunoblotting. Following IgG albumin depletion, the pooled proteins that were isolated from EV‐P of both groups were subjected to quantitative TMT proteomics. Results: Circulating term EV‐P isolated from both groups revealed ∼150 nm spherical vesicles containing CD9 and CD63 along with placental PLAP and HLA‐G proteins. Additionally, the concentration of EOPE‐derived EV‐P was significantly increased. A total of 208 proteins were identified, with 26 among them being differentially abundant in EV‐P of EOPE women. This study linked the pathophysiology of EOPE to 19 known and seven novel proteins associated with innate immune responses such as complement and TLR signaling along with hemostasis and oxygen homeostasis. Conclusion: The theory suggesting circulating EVs of placental origin could mimic molecular information from the parent organ—"the placenta"—is strengthened by this study. The findings pave the way for possible discovery of novel prognostic and predictive biomarkers as well as provide insight into the mechanisms driving the pathogenesis of EOPE. [ABSTRACT FROM AUTHOR]

We examined 164 pregnant women who were divided into three groups. Group I included 76 pregnant women (46.4 %) with euthyroid goiter of I–II degree. Group II consisted of 63 pregnant women (38.4 %) with subclinical hypothyroidism and diffuse thyroid goiter of I–II degree. Group III was the controls and consisted of 25 (15.2 %) pregnant women without thyroid pathology. The placenta was studied with the characteristics of ultrasound placentography, placental maturation disorders, the area and localization were determined, and pathological changes in the placental tissue were detected. Changes in the systolic-diastolic ratio in the uterine arteries and umbilical cord arteries were assessed, the resistance index in the uterine arteries, the pulsatile index in the fetal aorta and middle cerebral artery were determined using the method of color Doppler mapping of blood flow in the mother-placenta-fetus system. Study of the echographic picture of structural changes in the placenta revealed a significant impairment of its maturation, especially in the group with euthyroidism. Ultrasound screening revealed that in every second pregnant woman with thyroid disease, the condition of the placenta did not correspond to the gestational age, there were swelling, cysts and placental infarctions, a high frequency of diffuse changes in placental tissue, and hyperechogenic inclusions in the amniotic fluid. An increase in the resistance index in the uterine arteries of pregnant women, especially those with subclinical hypothyroidism, is noteworthy. With increasing gestational age, the peripheral resistance of the placental microvasculature increases due to involutional-dystrophic changes and circulatory disorders, which allows us to develop criteria for the prognosis and diagnosis of placental dysfunction, and to prevent perinatal disorders in pregnant women with thyroid disease. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a hypertensive condition that occurs during pregnancy and accounts for 2% to 8% of complications related to pregnancy globally. The diagnosis of preeclampsia is made when the blood pressure exceeds 140/90 mmHg after 20 weeks of pregnancy, occurring on two separate occasions with a minimum time gap of 4 hours, or exceeds 160/100 mmHg within a short period of time. Several biomarkers have been identified for prediction and diagnosis of preeclampsia. One of these biomarkers is Placental induced growth factor (PlGF), a factor that promotes angiogenesis, which belongs to the vascular endothelial growth factor family. Significantly reduced serum levels of placental growth factor (PIGF) have been observed in women diagnosed with preeclampsia compared to normotensive pregnancies. This study was designed to answer the question whether the measurement of PIGF at third trimester might be a predictive factor for the appearance of preeclampsia. Method: A comparative study was made on 40 women with PE and 40 age-gestational-age matched women without preeclampsia, as case and control, respectively. Levels of serum PIGF were measured, compared and its role in prediction of preeclampsia was studied. Results: The mean serum level of PIGF in cases was significantly lower (78.54±152.63pg/ml) than mean serum PIGF level of controls (553.73±263.27 pg./ml). When ROC analysis was done, PIGF =121.9pg/ml was found giving highest Youden index with sensitivity of 97.50%(95%CI-86.8 - 99.9), specificity of 100% (95%CI-91.2-100) and AUC of 0.97 (95% CI =0.91-0.99). Conclusion: Along with the hallmark symptoms of preeclampsia like high blood pressure and proteinuria, measurement of PIGF levels in late pregnant stage may be helpful in prediction of preeclampsia before actual onset of clinical symptoms which further assist in better diagnosis and management of disease. [ABSTRACT FROM AUTHOR]

Aim: Placenta accreta spectrum disorders (PAS) are a global threat to maternal well-being. The aim of this study was to assess differences in clinical characteristics and maternal outcomes between Turkish natives and Syrian refugees giving birth with a diagnosis of PAS at a tertiary centre, and to experience the management of this condition in the unique context of Türkiye, home to one of the world's largest refugee populations. Material and Method: A retrospective study was conducted using the medical records of 228 singleton pregnancies at high risk of PAS, between January 2019 and October 2022. PAS risk assessment was initially performed by ultrasound at mid-trimester, with diagnosis confirmed histologically or clinically, indicating the presence of placental retention following attempted manual removal. The study population was divided into two groups: native and refugee. We investigated disparities in demographic and medical characteristics and primary maternal and neonatal outcomes. Results: The study found an increased prevalence of previous cesarean delivery (p=0.005), anterior placenta (p<0.000), placenta previa (p=0.047), and deeper placental invasion (increta/percreta) (p<0.000) in the native group (n=161). The native group had a significantly higher rate of estimated blood loss (2093.5±1516.4 mL vs. 714.1±731.6 mL, p<0.000) and peripartum hysterectomy (p=0.005) compared to the refugee group (n=67). The refugee group had a notably higher incidence of delayed diagnosis (p<0.000) and a shorter surgery duration (p=0.027) compared to the native group. Conclusion: The current study highlights significant differences in patient characteristics and outcomes between native and refugee pregnant women with PAS. Despite facing challenges, these women did not encounter adverse perinatal outcomes, indicating the efficacy of healthcare interventions. [ABSTRACT FROM AUTHOR]

Background: Despite pregnancy's hypercoagulable state, the correlation between inherited thrombophilia and thrombotic adverse pregnancy outcomes remains uncertain. The objective of this study was to determine the prevalence of inherited thrombophilic polymorphisms among asymptomatic pregnant individuals and to examine their potential correlation with adverse perinatal outcomes. Methods: in this single-center prospective study, 105 healthy pregnant women were included. Genotyping was conducted for factor V Leiden (FVL), prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and plasminogen activator inhibitor-1 (PAI-1), alongside the assessment of protein C (PC), protein S (PS), and antithrombin (AT) levels. The study analyzed the association between inherited thrombophilic polymorphisms and pregnancy complications linked to placental insufficiency, such as gestational hypertension (GH), preeclampsia (PE), intrauterine death (IUD), fetal growth restriction (FGR), and placental abruption. Results: The prevalence of identifiable thrombophilic polymorphism mutations was 61.9% (95% confidence interval—CI 52.4–70.8%), with the most common single mutation being PAI-1 4G/5G (12/105, 11.4%, 95% CI 6.4–18.5). The most frequent combined mutation was heterozygosity for MTHFR C677T and PAI-1 (12/105, 11.4%, 95% CI 6.4–18.5). Notably, no FVL homozygous carriers or single homozygous and heterozygous carriers for prothrombin polymorphisms were found. Additionally, no deficiencies in PC and AT were detected among participants. Except for homozygosity for PAI-1, none of the studied polymorphisms demonstrated a significant association with pregnancy complications linked to placental insufficiency. Conclusions: The asymptomatic carriers of inherited thrombophilic polymorphisms do not have an increased risk of adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Pregnancy-related complications (PRC) impact maternal and fetal morbidity and mortality and place a huge burden on healthcare systems. Thus, effective diagnostic screening strategies are crucial. Currently, national and international guidelines define patients at low risk of PRC exclusively based on their history, thus excluding the possibility of identifying patients with de novo risk (patients without a history of disease), which represents most women. In this setting, previous studies have underlined the potential contribution of non-coding RNAs (ncRNAs) to detect patients at risk of PRC. However, placenta biopsies or cord blood samples are required, which are not simple procedures. Our review explores the potential of ncRNAs in biofluids (fluids that are excreted, secreted, or developed because of a physiological or pathological process) as biomarkers for identifying patients with low-risk pregnancies. Beyond the regulatory roles of ncRNAs in placental development and vascular remodeling, we investigated their specific expressions in biofluids to determine favorable pregnancy outcomes as well as the most frequent pathologies of pregnant women. We report distinct ncRNA panels associated with PRC based on omics technologies and subsequently define patients at low risk. We present a comprehensive analysis of ncRNA expression in biofluids, including those using next-generation sequencing, shedding light on their predictive value in clinical practice. In conclusion, this paper underscores the emerging significance of ncRNAs in biofluids as promising biomarkers for risk stratification in PRC. The investigation of ncRNA expression patterns and their potential clinical applications is of diagnostic, prognostic, and theragnostic value and paves the way for innovative approaches to improve prenatal care and maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Maternal vascular hypoperfusion is the most common cause of fetal growth restrict ion. Maternal oxidative status features are identifiable on placental pathology, and antepartum diagnostic methods are rapidly evolving. The current study was constructed to determine the maternal oxidative status by measuring serum ischemia modified albumin (IMA) levels in pregnancies complicated with idiopathic intrauterine growth restriction (IUGR). The current study was designed as a descriptive and cohort trial. A total of 87 pregnant women; 45 healthy controls and 42 pregnancies complicated with idiopathic IUGR were included to the study population. Maternal serum IMA concentration was measured prior to the administration of any medication. The perinatal outcomes of patie nts were also recorded. Maternal serum IMA concentration in pregnancies complicated by idiopathic IUGR was higher than in healthy controls. There was no significant difference between the groups (0.54±0.04 versus 0.55±0.06 ABSU, p: 0.314). IUGR is a significant pregnancy complication. Elevated oxidative stress which leads to an ischemic microenvironment is associated with IUGR. Maternal serum IMA which is a possible marker for oxidative stress is not increase in pregnancies complicated with idiopathic IUGR. [ABSTRACT FROM AUTHOR]

* Context.--Case studies reporting intraplacental choriocarcinoma (IPC) and intraplacental "chorangiocarcinoma" have recently increased, with IPC also represented in molecular analyses of gestational trophoblastic neoplasms. Objective.--To provide an overview of 2 intraplacental neoplastic lesions that can have a significant impact on both mother and fetus/infant, focusing on diagnostic characteristics, and ancillary and molecular tools that support diagnosis, determine prognosis, and further elucidate the nature of these lesions. Data Sources.--Data were compiled from a PubMed literature review that included diagnostic and additional keywords within the scope of study for gestational choriocarcinoma in general. Illustrative cases were retrieved from the pathology archives at Michigan Medicine, including the consultation files of the author. Conclusions.--Intraplacental gestational tumors exist along the spectrum of benign (chorangioma) to aggressive malignant (choriocarcinoma) neoplasms with a high potential for metastasis. Although most gestational choriocarcinomas follow complete hydatidiform mole, 20% to 25% occur in association with normal intrauterine gestations, including rare cases in which they are detected within the placenta (IPC). IPCs range from asymptomatic to widely metastatic, with metastases possible even when only microscopic IPCs are present. A second, even less common lesion, variably called "chorangiocarcinoma" and chorangioma with atypical trophoblast proliferation, is also reviewed. The incidence of these lesions is likely to be underestimated. Heightened suspicion and more liberal placental sampling, particularly when specific clinical features are present, may result in higher detection. Enhanced detection to provide the earliest intervention for both mother and infant may improve prognosis, particularly for asymptomatic disease that may later present with metastasis. [ABSTRACT FROM AUTHOR]

* Context.--Chronic histiocytic intervillositis (CHI) is a rare condition characterized by maternal immune cell infiltration into the human placenta. CHI is strongly associated with fetal growth restriction, miscarriage, and stillbirth, and knowledge of its etiology, and consequently effective treatment, is limited. Currently, diagnosis is largely subjective and varies between centers, making comparison between studies challenging. Objective.--To objectively quantify and interrelate inflammatory cells and fibrin in placentas with CHI compared with controls and determine how pathology may be altered in subsequent pregnancies following diagnosis. Macrophage phenotype was also investigated in untreated cases of CHI. Design.--Computerized analysis was applied to immunohistochemically stained untreated (index) cases of CHI, subsequent pregnancies, and controls. Index placentas were additionally stained by immunofluorescence for M1 (CD80 and CD86) and M2 macrophage markers (CD163 and CD206). Results.--Quantification revealed a median 32-fold increase in macrophage infiltration in index cases versus controls, with CHI recurring in 2 of 11 (18.2%) subsequent pregnancies. A total of 4 of 14 placentas (28.6%) with a diagnosis of CHI did not exhibit infiltration above controls. Macrophages in index pregnancies strongly expressed CD163. There was no significant difference in fibrin deposition between index cases and controls, although subsequent pregnancies displayed a 2-fold decrease compared with index pregnancies. CD31 T cells were significantly elevated in index pregnancies; however, they returned to normal levels in subsequent pregnancies. Conclusions.--In CHI, intervillous macrophages expressed CD163, possibly representing an attempt to resolve inflammation. Computerized analysis of inflammation in CHI may be useful in determining how treatment affects recurrence, and alongside pathologist expertise in grading lesion severity. [ABSTRACT FROM AUTHOR]

This study aims to report the treatment of retained placenta in a doe by administration of intrauterine antibiotics, accompanied by intramuscular injection of antibiotics, anti-inflammatory, and injection of vitamins A, D, and E as supportive treatment. The Saanen doe was brown, approximately two years old with a BCS of 3/5 and kidding for the first time on January 11, 2023. The following day, it was reported that the doe's placenta had not been expelled until 24 hours after kidding. Physically the doe was weak, unable to stand, and reddish-brown discharge was seen came out of the vulva. Based on these conditions the doe was diagnosed as having retained placenta with a fausta prognosis. The doe was treated with a bolus of antibiotics contained 250 mg sulphadiazine and 50 mg trimethoprim which was diluted with 5 mL of 0.9% NaCl for uterine lavage. Systemic treatment consisted of intramuscular injection of ceftiofur at 1.1 mg/kg bw, flunixin meglumine at 1.1 mg/kg bw, as well as a combination of 300,000 IU of vitamin A palmitate, 100,000 IU of vitamin D3, and 50 mg of vitamin E acetate as supportive treatment. The treatment was successful, the doe was able to stand and eat when examined the next day after treatment. The doe returned to estrus 42 days after treatment. It could be concluded that treatment of retained placenta in a doe with intrauterine broad-spectrum antibiotics, beta-lactamase antibiotics and intramuscular antiinflammatory, with vitamins A, D and E as supportive therapy was effective and the doe returned to estrus 42 days after treatment. [ABSTRACT FROM AUTHOR]

Aim: To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome. Methods: This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis. Results: Late-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA. Conclusions: HCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention. [ABSTRACT FROM AUTHOR]

Background: Because the cause of increasing rates of postpartum hemorrhage (PPH) and manual placental removal (MROP) is still unknown, we described trends in PPH, MROP, and childbirth interventions and examined factors associated with changes in rates of PPH and MROP. Methods: This nationwide cohort study used national perinatal registry data from 2000 to 2014 (n = 2,332,005). We included births of women who gave birth to a term singleton child in obstetrician‐led care or midwife‐led care. Multivariable logistic regression analyses were used to examine associations between characteristics and interventions, and PPH ≥ 1000 mL and MROP. Results: PPH rates increased from 4.3% to 6.6% in obstetrician‐led care and from 2.5% to 4.8% in midwife‐led care. MROP rates increased from 2.4% to 3.4% and from 1.0% to 1.4%, respectively. A rising trend was found for rates of induction and augmentation of labor, pain medication, and cesarean section, while rates of episiotomy and assisted vaginal birth declined. Adjustments for characteristics and childbirth interventions did not result in large changes in the trends of PPH and MROP. After adjustments for childbirth interventions, in obstetrician‐led care, the odds ratio (OR) of PPH in 2014 compared with the reference year 2000 changed from 1.66 (95% CI 1.57–1.76) to 1.64 (1.55–1.73) among nulliparous women and from 1.56 (1.47–1.66) to 1.52 (1.44–1.62) among multiparous women. For MROP, the ORs changed from 1.51 (1.38–1.64) to 1.36 (1.25–1.49) and from 1.56 (1.42–1.71) to 1.45 (1.33–1.59), respectively. Conclusions: Rising PPH trends were not associated with changes in population characteristics and rising childbirth intervention rates. The rising MROP was to some extent associated with rising intervention rates. [ABSTRACT FROM AUTHOR]

Background: Placental infarction refers to a localized area of ischemic villous necrosis resulting from the interruption of maternal blood flow to the intervillous space, which can be attributed to spasm, stenosis, or occlusion of the decidual spiral artery caused by systemic or localized maternal vascular disease. The presence of large placental infarcts may pose significant risks to fetal well-being, including intrauterine growth retardation, fetal distress, and even fetal demise. Although placental infarction is commonly identified during postnatal pathological examinations, its prenatal diagnosis through ultrasound remains challenging and has been rarely reported. Case Presentation: This report presents a case of acute placental infarction diagnosed by prenatal ultrasound using Superb Micro-vascular Imaging (SMI) technology. At 23 weeks' gestation, the ultrasound revealed that the placenta was attached to the left lateral and posterior walls of the uterus, showing localized thickening. Within this area of thickening, there were observed inhomogeneous hypoechoic regions. Superb Micro-vascular Imaging (SMI) revealed an abnormal echogenic region within the thickened placental tissue that lacked microvascular blood flow signals, but showed surrounding vascularity. Visually, this elliptical-shaped echogenic region enveloped by microvascular blood flow. From the 29th weeks of gestation onward, ultrasound suggested that the fetus was small for gestational age. A live baby weighing 2360g was delivered by cesarean section at 37 weeks' gestation. The placenta was approximately 20× 18 × 3 cm with large grayish-yellow infarcts. Conclusion: SMI allows rapid screening of large placental infarcts and easy detection of regions without normal vessel trees, thereby reducing missed diagnoses. Infarct area is easily measured by measuring the area surrounded by small blood vessels, especially in acute placental infarction, which is very helpful in accurately determining infarct size. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy's hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations. The use of TEG/ROTEM for assessing the hemostatic profile of PE women has been little considered, even though conventional coagulation tests (CCTs) have not helped to monitor hemostasis in this population. Compared with normal pregnancy, TEG/ROTEM in PE reveals an excessive hypercoagulability analogous with the severity of the disease, characterized by higher-stability fibrin clots. The TEG/ROTEM parameters can reflect PE severity and may be used for monitoring and as predictive markers for the disease. [ABSTRACT FROM AUTHOR]

Introduction: Infection by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been shown to affect multiple organs in the human body. Research shows that Coronavirus Disease (COVID-19)-positive pregnant women experience poorer perinatal outcomes related to placental infection, including higher risks of miscarriage, preeclampsia, preterm birth, and stillbirth. Aim: To evaluate the histopathological changes in the placentas of COVID-19-positive mothers and the associated foetal outcomes. Materials and Methods: This cohort study was conducted at Kalinga Institute of Medical Sciences (KIMS) Bhubaneswar, Odisha, India, over a period of one year and eight months, from November 2020 to July 2022. It included 23 COVID-19-positive pregnant females admitted for safe confinement during the first and second COVID-19 waves. Thirty COVID-19-negative pregnant women admitted for safe delivery during the same period served as controls. Placentas were collected, processed, and stained according to standard protocols. Descriptive data were interpreted as frequencies and percentages, and associations were tested using the Chi-square test. A p-value <0.05 was considered statistically significant. Results: The study included 23 cases (mean gestational age: 37 weeks and 5 days) and 30 controls (mean gestational age: 38 weeks and 6 days). The prevalence of Maternal Vascular Malperfusion (MVM) and Foetal Vascular Malperfusion (FVM) was found to be higher among cases than controls. Conclusion: Compared to controls, COVID-19-positive placentas showed a higher prevalence of both MVM and FVM. This might be attributable to the hypercoagulable state associated with COVID-19. Further research is needed to explore the potential effects of intrauterine inflammation on neonates exposed to COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as a 'preeclampsia‐like syndrome'. However, the mechanisms underpinning SARS‐CoV‐2‐induced placental malfunction are still unclear. Here, we investigated whether the transcriptional architecture of the placenta is altered in response to SARS‐CoV‐2 infection. Methods: We utilised whole‐transcriptome, digital spatial profiling, to examine gene expression patterns in placental tissues from participants who contracted SARS‐CoV‐2 in the third trimester of their pregnancy (n = 7) and those collected prior to the start of the coronavirus disease 2019 (COVID‐19) pandemic (n = 9). Results: Through comprehensive spatial transcriptomic analyses of the trophoblast and villous core stromal cell subpopulations in the placenta, we identified SARS‐CoV‐2 to promote signatures associated with hypoxia and placental dysfunction. Notably, genes associated with vasodilation (NOS3), oxidative stress (GDF15, CRH) and preeclampsia (FLT1, EGFR, KISS1, PAPPA2) were enriched with SARS‐CoV‐2. Pathways related to increased nutrient uptake, vascular tension, hypertension and inflammation were also enriched in SARS‐CoV‐2 samples compared to uninfected controls. Conclusions: Our findings demonstrate the utility of spatially resolved transcriptomic analysis in defining the underlying pathogenic mechanisms of SARS‐CoV‐2 in pregnancy, particularly its role in placental dysfunction. Furthermore, this study highlights the significance of digital spatial profiling in mapping the intricate crosstalk between trophoblasts and villous core stromal cells, thus shedding light on pathways associated with placental dysfunction in pregnancies with SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

The most common association related to alpha-fetoprotein (AFP) is fetal neural tube defect (NTD), and indeed, this is where the international career of this protein began. In times when ultrasonography was not yet technically advanced, the detection of high levels of AFP in maternal serum (MS-AFP) and amniotic fluid was the basis for suspecting neural tube defects. In cases where there was no confirmation of NTD, other causes were sought. It has been established that high titers of MS-AFP could originate in other defects or diseases, such as (1) increased proteinuria in severe fetal kidney diseases; (2) pathological overproduction in liver diseases; (3) penetration through the membranes of gastrointestinal organs exposed to amniotic fluid; (4) passage through the walls of skin vessels; and as a side effect of (5) hepatic hematopoiesis and increased transfer through the edematous placenta in fetal anemia. This article provides a review of the current literature on congenital defects and genetic diseases in the fetus where an elevated level of MS-AFP may serve as the initial diagnostic clue for their detection. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to estimate the association between arcuate uterus and pregnancy outcomes using controls selected from a similarly high-risk cohort. Study Design This is a retrospective cohort study of women with an arcuate uterus cared for by a single maternal–fetal medicine practice from 2005 to 2020. We included all women with a singleton pregnancy ≥20 weeks and diagnosis of arcuate uterus and randomly selected (3:1) patients with a singleton pregnancy and no uterine anomaly from the same practice as controls. Baseline characteristics and pregnancy outcomes were compared between the two groups. Chi-square, Fisher's exact, and independent samples t -test were used for data analysis, as indicated. Results A total of 37 women with an arcuate uterus (55 independent singleton pregnancies) and 165 controls were included. There were no differences in baseline characteristics. Women with an arcuate uterus had a significantly higher rate of spontaneous preterm birth less than 37 weeks (10.9 vs. 3.0%, p = 0.031) and were more likely to require vaginal progesterone (5.5 vs. 0.6%, p = 0.049) and administration of antenatal corticosteroids (16.4 vs. 5.5%, p = 0.020). Arcuate uterus was also associated with lower birthweight (3,028.1 ± 528.0 vs. 3257.2 ± 579.9 g, p = 0.010) and higher incidence of intrauterine fetal growth restriction (20.0 vs. 7.3%, p = 0.008), despite similar starting body mass index (BMI) and weight gain throughout pregnancy. There were no differences in preeclampsia, malpresentation, cesarean delivery, blood transfusion, retained placenta, or morbidly adherent placenta. Conclusion Arcuate uterus is associated with a significantly increased risk of spontaneous preterm birth (<37 weeks), need for vaginal progesterone for short cervix and antenatal corticosteroids, fetal growth restriction, and lower mean birthweight. These findings suggest that arcuate uterus is not just a normal variant of uterine anatomy but rather a risk factor for poor fetal growth, short cervix, and a higher risk pregnancy. Key Points Arcuate uterus is associated with increased risk of preterm birth and fetal growth restriction. Women with arcuate uteri had higher rates of vaginal progesterone use during pregnancy. Arcuate uterus should be treated as a true finding rather than a normal anatomical variant. [ABSTRACT FROM AUTHOR]

Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum. [ABSTRACT FROM AUTHOR]

Background The spectrum of placental adhesive disorders (PAD) forms an important cause for emergency cesarean hysterectomy, requiring an accurate prenatal diagnosis for optimal obstetric management. Purpose The aim of this study was to assess the utility of magnetic resonance imaging (MRI) and to identify the individual MRI features that are most useful in the evaluation of PAD. Materials and Methods This was a retrospective review of the MRI of 24 women with abnormal placentation, confirmed using histopathology/intraoperative findings as the reference standard. Patients were categorized as negative or positive for PAD (placenta accreta, increta, and percreta) on MRI and compared with the reference standard. We assessed the diagnostic performance of MRI and the features that best correlated with the presence of PAD. Results Among the 24 women (mean age: 29.8 years) with risk factors, 16 had PAD (6 accreta, 7 increta, and 3 percreta). There was a history of previous lower segment cesarean section and placenta previa in 14 (87.5%). MRI could identify the presence of PAD in all (100% sensitivity) and its absence in three out of eight patients (37.5% specificity). The features with highest sensitivity were intraplacental dark bands (100%), myometrial thinning/loss of interface with myometrium (100%), placental heterogeneity (75%), and uterine contour abnormality (75%). Conclusion MRI is an important modality for the investigation of PAD in suspected cases, with excellent sensitivity and good accuracy. Identifying the presence of risk factors, low-signal-intensity bands, and thinning/loss of placental–myometrial interface will aid in its diagnosis. [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]

The article focuses on the discovery of a placental mass during pregnancy and its potential implications on fetal health. Topics include the differential diagnosis for a mass on or near the placenta, which includes chorionic cyst, chorangioma, and thrombosis or hematoma of the umbilical vessels, and the significance of large placental masses in potentially causing intrauterine growth restriction and other complications.

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]

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Placental neovascularization plays a crucial role in fetomaternal circulation throughout pregnancy and is dysregulated in several pregnancy-related diseases, including preeclampsia, gestational diabetes mellitus, and fetal growth restriction. Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that differentiate into mature endothelial cells, which influence vascular homeostasis, neovascularization, and endothelial repair. Since their discovery in 1997 by Asahara et al., the role of EPCs in vascular biology has garnered a lot of interest. However, although pregnancy-related conditions are associated with changes in the number and function of EPCs, the reported findings are conflicting. This review discusses the discovery, isolation, and classification of EPCs and highlights discrepancies between current studies. Overviews of how various diseases affect the numbers and functions of EPCs, the role of EPCs as biomarkers of pregnancy disorders, and the potential therapeutic applications involving EPCs are also provided. [ABSTRACT FROM AUTHOR]

Circulating miRNAs the in blood are promising biomarkers for predicting pregnancy complications and adverse birth outcomes. Previous work identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following prenatal alcohol exposure and regulated epithelial–mesenchymal transition in the placenta. Here we show that a single intravascular administration of pooled murine-conserved HEamiRNAs to pregnant mice on gestational day 10 (GD10) attenuates umbilical cord blood flow during gestation, explaining the observed intrauterine growth restriction (IUGR), specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of members of the Notch pathway (Dll4, Rfng, Hey1), which is a pathway important for trophoblast migration and differentiation. Weighted gene co-expression network analysis also identified chemokine signaling, which is responsible for regulating immune cell-mediated angiogenesis in the placenta, as an important predictor of fetal growth and head size. Our data suggest that HEamiRNAs perturb the expression of placental genes relevant for angiogenesis, resulting in impaired umbilical cord blood flow and subsequently, IUGR. [ABSTRACT FROM AUTHOR]

To investigate the incidence and risk factors of bilobate placenta, as well as to assess its impact on preeclampsia (PE), preterm delivery (PTD) and small-for-gestational age (SGA) neonates. A prospective study of singleton pregnancies, undergoing routine anomaly scan at 20+0–23+6 gestational weeks, was conducted, between 2018 and 2022. The impact of prenatally diagnosed bilobate placenta on PE, PTD and SGA was assessed. Multivariate logistic regression models were employed to assess the independent association between bilobate placenta and the main pregnancy outcomes, using specific confounders. Additionally, a risk factor analysis was performed. The study population included 6,454 pregnancies; the incidence of prenatally diagnosed bilobate placenta was 2.0 % (n=129). Bilobate placenta was associated with PE (aOR: 1.721; 95 % CI: 1.014–2.922), while no statistically significant association was found between this anatomical variation and SGA (aOR: 1.059; 95 % CI: 0.665–1.686) or PTD (aOR: 1.317; 95 % CI: 0.773–2.246). Furthermore, pregnancies with prenatally diagnosed bilobate placenta had an increased prevalence of abnormal cord insertion (marginal or velamentous) (9.8 vs. 27.1 %; p<0.001) and increased mean UtA PI z-score (0.03 vs. 0.23; p=0.039). Conception via ART (aOR: 3.669; 95 % CI: 2.248–5.989), previous history of 1st trimester miscarriage (aOR: 1.814; 95 % CI: 1.218–2.700) and advancing maternal age (aOR: 1.069; 95 % CI: 1.031–1.110) were identified as major risk factors for bilobate placenta. Bilobate placenta, excluding cases of co-existing vasa previa, is associated with higher incidence of PE, increased mean UtA PI z-score and higher probability of abnormal cord insertion, but not with increased risk for SGA or PTD. It is more common in pregnancies following ART and in women with a previous 1st trimester miscarriage. [ABSTRACT FROM AUTHOR]

To compare the clinical and morphological characteristics of the "mother-placenta-fetus" system in high risk pregnant women of three groups: no SARS-CoV-2 infection, mild SARS-CoV-2 infection, and severe SARS-CoV-2 infection. A case-control study was performed for all deliveries, at 28 weeks' gestation or greater, who had standard indications for placental pathologic examination. Three groups were formed: (1) control group (no SARS-CoV-2 infection), (2) mild SARS-CoV-2 infection, (3) severe SARS-CoV-2 infection. High-risk pregnancies were registered in all cases in the study groups. The examination of the placenta and the selection of fragments of placental tissue were carried out in accordance with the consensus recommendations of the Amsterdam Placental Workshop Group. The sections were subjected to standard processing and stained with hematoxylin and eosin according to the standard protocol. All cases were reviewed by two pathologists, which did not know any information on pregnancy outcome and clinical data. Statistical analysis was performed using SPSS, p<0.05 was considered statistically significant. Women with severe SARS-CoV-2 infection had an increased rate of multimorbidity including diabetes, chronic hypertension and obesity (p<0.01) compared with the other groups. Placentas at severe COVID-19 course were damaged by both chronic and acute injuries, in comparison to the mild and control groups (p<0.001). Also an important finding in severe COVID-19 was diffuse necrosis of the villous trophoblast – homogenization, diffuse circular eosinophilic masses surrounding the chorionic villi. Women with multimorbidity are an "at-risk" subgroup for severe SARS-CoV-2 infection and greater likelihood of both placental damage and perinatal hypoxic-ischemic events. These results suggest that patient education, SARS-CoV-2 disease monitoring and preventive measures would be of benefit to this group. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case–control study design. Cases (n = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21–5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22–4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05–11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD. [ABSTRACT FROM AUTHOR]

Background and purpose: Placental thickness measured at the level of the umbilical cord insertion can be used as a new parameter to estimate gestational age. The present study was undertaken to evaluate the relationship between placental thickness and gestational age and to assess the growth pattern of placenta with advancing gestational age in pregnancy induced hypertension and gestational diabetes mellitus. Objectives: 1. To assess the placental thickness in normal pregnancy, Pregnancy induced hypertension and gestational diabetes mellitus 2. To compare the placental thickness in normal pregnancy with placental thickness in gestational diabetes mellitus and in pregnancy induced hypertension. Methods: The study included 120 antenatal cases of gestational age between 24-28 weeks of gestation based on each 40 cases of normal pregnancy, gestational diabetes mellitus and pregnancy induced hypertension women aged between 18-40 years, who attending Adichunchanagiri Institute of Medical Sciences and referred to the Radiodiagnosis department for antenatal Ultrasound from the period of November 2019 to May 2020 The study mainly aimed at detailed assessment of placental thickness in normal pregnancy, pregnancy induced hypertension and gestational diabetes mellitus to assess the spectrum of placental changes and to correlate these findings with severity and duration of maternal disease and with the fetal outcome. A study of 120 pregnant patients were done with the collaboration of Department of Obstetrics and Gynecology, to find out the thickness of placenta in pregnancy induced hypertension, gestational diabetes mellitus and normal pregnancy. Mean placental thickness found to be much lower in the study group of pregnancy induced hypertension and increased in gestational diabetes mellitus in comparison to placental thickness of normal pregnancy. Placental thickness of normal pregnancy corresponds to the gestational age with normal fetal outcome. Multiparous women with increasing age groups were more likely to have gestational diabetes mellitus than primi-gravida women. Conclusion: To conclude on the outcome received in our study signifies placental thickness can be used as an accurate indicator for estimating the fetal and maternal well-being. The variations in placental thickness decide whether a fetus is considered to be at risk. Also in our study the thickness of placenta did not show any variation with the location of placenta. Abnormal placental thickness in the early stages helps to detect intrauterine growth restriction (IUGR) and gestational diabetes mellitus(GDM). In normal pregnancy the placental thickness almost corresponds to the gestational age and results in healthy fetus and mother. In GDM the placenta thickness appears thickened and undergoes alterations in its formation, structure, and function. According to the review, these alterations are related to an oxygenation deficiency in the fetus, changes in the transplacental transport of nutrients and other alterations that cause fetal overgrowth by increasing their availability, and other consequences to the developing fetus. Placental thickness is reduced in pregnancy induced hypertension due to increased blood pressure. Pregnancy induced hypertension, produces accelerated maturation and rapid aging of the chorionic villi with the risk of inducing a placental abruption. In addition, placental circulation is reduced causing decrease in oxygen saturation of the fetus. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed. Methods: Single-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte. Results: A total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation. Conclusions: We revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target. [ABSTRACT FROM AUTHOR]

Summary: In fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti‐HPA‐1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C‐reactive protein, soluble CD14, procalcitonin, and sFlt‐1 did not differ between the two cohorts. There was no correlation between C‐reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt‐1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt‐1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT. [ABSTRACT FROM AUTHOR]

Background: Many pathological insults are associated with elevation of blood pressure levels during pregnancy resulting in a difficult pregnancy and a poor outcome on both mother and baby. Objective: In this study, we examine the histological and immunohistochemical markers of the placentae in cases of hypertension in pregnancy and preeclampsia and compared them to a placenta of normal pregnancy among a random sample of Iraqi pregnant women. Materials and Methods: Ninety women divided into three groups, 30 in each, selected with straightforward pregnancies (Group A), mothers with pregnancy-induced hypertension (Group B), and preeclamptic mothers (Group C) were chosen from the indoor patients of the gynecology and obstetrics department of Al-Khansaa teaching hospital in Mosul for placental tissues examination. Histological examination was done by using hematoxylin and eosin stain (H & E), and immunohistochemistry was achieved by using immunohistochemical markers named: insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (b-FGF) markers, which are expressed in placental tissues. Results: Different changes were observed in the placentae affected when compared with normal one, such as syncytial knots formation, thickening of trophoblastic basement membrane, cytotrophoblastic cellular proliferation, fibrinoid necrosis, endothelial proliferation, calcified and hyalinised villous spots, villous edema, and atherosis of the uteroplacental arteries. Significant immunohistochemical changes were obtained when compared with normal placentae where elevation of both b-FGF and IGF-1 in preeclamptic placentae was observed when compared to hypertensive and control cases. Conclusion: Significant changes appeared in the placentae of hypertensive and preeclamptic mothers, both in histological and immunohistochemical examinations. [ABSTRACT FROM AUTHOR]

Background: Pregnant women have an increased risk of getting infected with SARS-CoV-2 and are more prone to severe illness. Data on foetal demise in affected pregnancies and its underlying aetiology is scarce and pathomechanisms remain largely unclear. Case: Herein we present the case of a pregnant woman with COVID-19 and intrauterine foetal demise. She had no previous obstetric or gynaecological history, and presented with mild symptoms at 34 + 3 weeks and no signs of foetal distress. At 35 + 6 weeks intrauterine foetal death was diagnosed. In the placental histopathology evaluation, we found inter- and perivillous fibrin depositions including viral particles in areas of degraded placental anatomy without presence of viral entry receptors and SARS-CoV-2 infection of the placenta. Conclusion: This case demonstrates that maternal SARS-CoV-2 infection in the third trimester may lead to an unfavourable outcome for the foetus due to placental fibrin deposition in maternal COVID-19 disease possibly via a thrombogenic microenvironment, even when the foetus itself is not infected. Novelty: Symptomatic COVID-19 of the mother may cause microthrombotic events in the placenta. These microthrombotic events may lead to placental insufficiency and reduced growth velocity. Further systematic clinical studies investigating the thrombogenic effect of a SARS-CoV-2 infection in pregnancy are warranted. Although a single case report, the findings support previous concerns about placental insufficiency after SARS-CoV-2 infection. This report adds to existing literature and could help support recommendations for additional antenatal testing in similar settings. [ABSTRACT FROM AUTHOR]

Background: Placental dysfunction, a root cause of common syndromes affecting human pregnancy, such as preeclampsia (PE), fetal growth restriction (FGR), and spontaneous preterm delivery (sPTD), remains poorly defined. These common, yet clinically disparate obstetrical syndromes share similar placental histopathologic patterns, while individuals within each syndrome present distinct molecular changes, challenging our understanding and hindering our ability to prevent and treat these syndromes. Methods: Using our extensive biobank, we identified women with severe PE (n = 75), FGR (n = 40), FGR with a hypertensive disorder (FGR + HDP; n = 33), sPTD (n = 72), and two uncomplicated control groups, term (n = 113), and preterm without PE, FGR, or sPTD (n = 16). We used placental biopsies for transcriptomics, proteomics, metabolomics data, and histological evaluation. After conventional pairwise comparison, we deployed an unbiased, AI-based similarity network fusion (SNF) to integrate the datatypes and identify omics-defined placental clusters. We used Bayesian model selection to compare the association between the histopathological features and disease conditions vs SNF clusters. Results: Pairwise, disease-based comparisons exhibited relatively few differences, likely reflecting the heterogeneity of the clinical syndromes. Therefore, we deployed the unbiased, omics-based SNF method. Our analysis resulted in four distinct clusters, which were mostly dominated by a specific syndrome. Notably, the cluster dominated by early-onset PE exhibited strong placental dysfunction patterns, with weaker injury patterns in the cluster dominated by sPTD. The SNF-defined clusters exhibited better correlation with the histopathology than the predefined disease groups. Conclusions: Our results demonstrate that integrated omics-based SNF distinctively reclassifies placental dysfunction patterns underlying the common obstetrical syndromes, improves our understanding of the pathological processes, and could promote a search for more personalized interventions. [ABSTRACT FROM AUTHOR]

The original SARS-CoV-2 lineages have been replaced by successive variants of concern (VOCs) over time. The aim of this study was to perform an assessment of the placental infection by SARS-CoV-2 according to the predominant variant at the moment of COVID-19 diagnosis. This was a prospective study of SARS-CoV-2-positive pregnant women between March 2020 and March 2022. The population was divided into pregnancies affected by COVID-19 disease during 2020 (Pre-VOC group) and pregnancies affected after December 2020 by SARS-CoV-2 variants of concern (VOC group). The presence of virus was assessed by RT-PCR, and the viral variant was determined by whole genome sequencing. A total of 104 placentas were examined, among which 54 cases belonged to the Pre-VOC group and 50 cases belonged to the VOC group. Sixteen positive placental RT-PCR tests for SARS-CoV-2 were reported. The NGS analysis confirmed the SARS-CoV-2 lineage in placenta tissue. All samples corresponded to the Pre-VOC group, whereas no placental presence of SARS-CoV-2 was detected in the VOC group (16, 29.6% vs. 0, 0.0% p = 0.000). Preterm birth (9, 16.7% vs. 2, 4%; p = 0.036) and hypertensive disorders of pregnancy (14, 25.9% vs. 3, 6%; p = 0.003) were more frequent in the Pre-VOC group than in the VOC group. Finally, the VOC group was composed of 23 unvaccinated and 27 vaccinated pregnant women; no differences were observed in the sub-analysis focused on vaccination status. In summary, SARS-CoV-2-positive placentas were observed only in pregnancies infected by SARS-CoV-2 wildtype. Thus, placental SARS-CoV-2 presence could be influenced by SARS-CoV-2 variants, infection timing, or vaccination status. According to our data, the current risk of SARS-CoV-2 placental infection after maternal COVID disease during pregnancy should be updated. [ABSTRACT FROM AUTHOR]

Objective Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts, chorionic microcysts in the membranes and chorionic disc, and decidual clusters of multinucleate trophoblasts. The histological lesions were previously and individually reported in association with various clinical and placental abnormalities. This retrospective statistical analysis of a large placental database from high-risk pregnancy statistically compares placentas with and without a composite group of features of SPI. Study Design Twenty-four independent abnormal clinical and 44 other than SPI placental phenotypes were compared between 4,930 placentas without (group 1) and 1,283 placentas with one or more histological features of SPI (composite SPI group; group 2). Placentas were received for pathology examination at a discretion of obstetricians. Placental lesion terminology was consistent with the Amsterdam criteria, with addition of other lesions described more recently. Results Cases of group 2 featured statistically and significantly (p < 0.001after Bonferroni's correction) more common than group 1 on the following measures: gestational hypertension, preeclampsia, oligohydramnios, polyhydramnios, abnormal Dopplers, induction of labor, cesarean section, perinatal mortality, fetal growth restriction, stay in neonatal intensive care unit (NICU), congenital malformation, deep meconium penetration, intravillous hemorrhage, villous infarction, membrane laminar necrosis, fetal blood erythroblastosis, decidual arteriopathy (hypertrophic and atherosis), chronic hypoxic injury (uterine and postuterine), intervillous thrombus, segmental and global fetal vascular malperfusion, various umbilical cord abnormalities, and basal plate myometrial fibers. Conclusion SPI placentas were statistically and significantly associated with 48% abnormal independent clinical and 51% independent abnormal placental phenotypes such as acute and chronic hypoxic lesions, fetal vascular malperfusion, umbilical cord abnormalities, and basal plate myometrial fibers among others. Therefore, SPI should be regarded as a category of placental lesions related to maternal vascular malperfusion and the "Great Obstetrical Syndromes." Key Points SPI reflects abnormal distribution of extravillous trophoblasts. SPI features abnormal clinical and placental phenotypes. SPI portends increased risk of complicated perinatal outcome. [ABSTRACT FROM AUTHOR]

Aim: The ongoing global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has generated significant apprehensions in maternalfetal medicine. Initially considered to affect the respiratory system primarily, recent findings have indicated that the pandemic has far-reaching implications for various physiological functions, particularly in pregnant individuals. This study focused on examining the influence of COVID-19 on placental histopathology in pregnant women infected with SARS-CoV-2. Material and Methods: We conducted a comparative study involving two groups of pregnant women with similar demographic characteristics: a group testing positive for COVID-19 (n=31) and a control group of COVID-19-negative pregnant women (n=31). After delivery, placental tissues were collected and subjected to comprehensive histopathological examination to determine any potential alterations in the placenta induced by SARS-CoV-2 infection. Results: Our study revealed substantial histopathological alterations in pregnant women with COVID-19 placentas. Notably, the COVID-19 group displayed a higher incidence of cesarean deliveries, possibly due to concerns related to maternal-fetal transmission and respiratory complications. Furthermore, neonates born to mothers in the COVID-19 group had significantly lower birth weights. Several placental histopathological changes, including villous fibrin deposits, thrombosis, intervillous hemorrhage, agglutination, avascular fibrotic villi, and syncytial knots, were markedly increased in the COVID-19 group, indicating compromised fetal blood circulation. Although not statistically significant, trends toward elevated villous infarction, fetal vascular malperfusion, and chorioamnionitis were observed. Conclusion: Our study underscores the potential risks associated with COVID-19 on placental health, maternal well-being, and neonatal outcomes. We must understand the underlying physiological mechanisms behind these pathological changes to provide optimal maternal-fetal care during this ongoing crisis. Comprehensive and multicentric studies are urgently required to confirm and expand our findings. [ABSTRACT FROM AUTHOR]

Regarding the hypertensive disorders of pregnancy, pre-eclampsia (PE) remains one of the leading causes of severe and life-threatening maternal and fetal complications. Screening of early-onset PE (<34 weeks of pregnancy), as well as late-onset PE (≥34 weeks), shows poor performance if based solely on clinical features. In recent years, biochemical markers from maternal blood—the pro-angiogenic protein placental growth factor (PlGF) and the antiangiogenic protein soluble FMS-like tyrosine kinase 1 (sFlt-1)—and Doppler velocimetry indices—primarily the mean uterine pulsatility index (PI), but also the uterine resistivity index (RI), the uterine systolic/diastolic ratio (S/D), uterine and umbilical peak systolic velocity (PSV), end-diastolic velocity (EDV), and uterine notching—have all shown improved screening performance. In this review, we summarize the current status of knowledge regarding the role of biochemical markers and Doppler velocimetry indices in early prediction of the onset and severity of PE and other placenta-related disorders, as well as their role in monitoring established PE and facilitating improved obstetrical surveillance of patients categorized as high-risk in order to prevent adverse outcomes. A sFlt-1/PlGF ratio ≤ 33 ruled out early-onset PE with 95% sensitivity and 94% specificity, whereas a sFlt-1/PlGF ≥88 predicted early-onset PE with 88.0% sensitivity and 99.5% specificity. Concerning the condition's late-onset form, sFlt-1/PlGF ≤ 33 displayed 89.6% sensitivity and 73.1% specificity in ruling out the condition, whereas sFlt-1/PlGF ≥ 110 predicted the condition with 58.2% sensitivity and 95.5% specificity. The cut-off values of the sFlt-1/PlGF ratio for the screening of PE were established in the PROGNOSIS study: a sFlt-1/PlGF ratio equal to or lower than 38 ruled out the onset of PE within one week, regardless of the pregnancy's gestational age. The negative predictive value in this study was 99.3%. In addition, sFlt-1/PlGF > 38 showed 66.2% sensitivity and 83.1% specificity in predicting the occurrence of PE within 4 weeks. Furthermore, 2018 ISUOG Practice Guidelines stated that a second-trimester mean uterine artery PI ≥ 1.44 increases the risk of later PE development. The implementation of a standard screening procedure based on the sFlt-1/PlGF ratio and uterine Doppler velocimetry may improve early detection of pre-eclampsia and other placenta-related disorders. [ABSTRACT FROM AUTHOR]