Perivillous Fibrin Deposition Research Articles

Expression of CD68 by macrophages and histopathology of the placenta in COVID-19: association with obstetric and neonatal complications

Introduction. COVID-19 causes direct and indirect placental damage through inflammatory monocytes/ macrophages, increasing the risk of infectious and inflammatory diseases in newborns.Aim. To analyze the expression of CD68 by macrophages and structural changes in the placenta, and to assess the risks of obstetric and neonatal complications in cases of moderate COVID-19 during the third trimester of pregnancy.Materials and methods. A histological examination was conducted on 33 placentas from women with moderate COVID-19 in the third trimester of pregnancy and 30 placentas from women not infected with SARS-CoV-2. Tissue sections were analyzed using an automated microscopy system for histological studies. CD68 expression on placental macrophages was studied using flow cytometry. Detection of SARS-CoV-2 RNA in placental tissue samples, as well as in nasopharyngeal swabs from newborns, was carried out by real-time reverse transcription polymerase chain reaction (RT-PCR).Results. An increase in the number of CD68-positive macrophages was observed in the placentas from women with COVID-19 (80.8 (78.2; 83.5) %; p<0.0001) compared to samples from women not infected with SARS-CoV-2 (19.6 (17.2; 21.8) %). All placental samples and nasopharyngeal swabs from newborns of mothers with COVID-19 tested negative for SARS-CoV-2, indicating a low risk of vertical transmission. Histological analysis revealed signs of infectious involvement of both maternal and fetal placental parts, including focal deciduitis, villitis, and histiocytic intervillositis. Circulatory disorders were characterized by decidual vasculopathy, accelerated villous maturation, perivillous fibrin deposition, thrombosis, villous necrosis, and an increase in syncytial knots. A link was established between structural placental abnormalities and the development of chronic placental insufficiency (relative risk (RR)=2.33), preterm birth and premature rupture of membranes (RR=4.26), and fetal growth restriction. Newborns from mothers with COVID-19 exhibited complications such as cerebral ischemia and respiratory distress syndrome.Conclusion. Moderate COVID-19 in the third trimester of pregnancy can induce structural changes in the placenta, reflecting both compensatory-adaptive responses and inflammation driven by CD68-expressing macrophages. These alterations are associated with a high risk of obstetric and neonatal complications.

Massive perivillous fibrin deposition: A case report

Massive perivillous fibrin deposition: A case report

Placental lesions in systemic lupus erythematosus pregnancies associated with small for gestational age infants.

Up to a quarter of pregnant individuals with SLE have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE. We retrospectively analysed SLE deliveries with placental analysis at UCSD from November 2018 to October 2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE. Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, P = 0.01), placental disc infarct (50% vs 6%, P = 0.02) and increased perivillous fibrin deposition (PVFD, 58% vs 0%, P = 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, P = 0.03). The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies and correlation to adverse outcomes.

Effects of apelin on neonatal brain neurogenesis in L-NAME-induced maternal preeclampsia

The aim of this study was to investigate the possible protective effects of apelin, which is known to have antioxidant and anti-inflammatory effects, on changes in neurogenesis in newborns of pregnant rats with L-NAME-induced preeclampsia. Wistar albino female rats were divided into four experimental groups: Control, Apelin, Preeclampsia and Preeclampsia + Apelin. Blood pressure was measured on the 5th, 11th and 17th days of gestation, urine protein was analyzed from urine samples collected for 24 h on the 6th, 12th and 18th days and serum creatinine was analyzed from serum samples. Maternal kidney and placenta tissues were obtained to establish the preeclampsia model, and neonatal brain tissues including the cortex, hippocampus and cerebellum regions were obtained to investigate neurogenesis and examined by histological and immunohistochemical methods. The number of newborns, body weight and brain weight of the newborns were measured. eNOS, IL-10, nNOS and NO levels in the brain analyzed via ELISA. Mean arterial pressure, urine protein and serum creatinine increased in the preeclampsia. Newborn weight decreased in the Preeclampsia group, the values in the Preeclampsia + Apelin group were closer to the Control and Apelin groups. In the Preeclampsia group, edema and dilatation in the proximal and distal tubules of kidneys, perivillous fibrin deposition and increase in syncytial nodules of placenta were observed. VEGF immunoreactivity decreased and iNOS immunoreactivity increased in both kidney and placenta. In neonatal brain tissue examinations, cytotoxic edema accompanied by thinning of cortex, delayed migration and lower cell counts in the hippocampus, and increase in intercellular spaces and EGL thickening in the cerebellum were observed in the preeclampsia. Expression of NeuN, GFAP, MBP, IL-10, eNOS, nNOS and NO levels decreased, whereas expression of Iba-1 increased in the preeclampsia. In the Preeclampsia + Apelin group, these findings were similar to the Control and Apelin groups. Apelin administration was found to be beneficial for preventing the adverse consequences of preeclampsia, but further experimental and clinical studies are needed to better understand these effects.

Ultrasound findings in pregnancies affected by placental perivillous fibrin deposition: A case series

Ultrasound findings in pregnancies affected by placental perivillous fibrin deposition: A case series

Prevalence and association of placental lesions with obstetrical features and outcome: data from French prospective study

Since the Consensus Statement diffused by the Amsterdam Placental Workshop Group, knowledge of the meaning of placental vascular malperfusion has become essential in the unavoidable analysis of obstetrical history in a patient followed for autoimmune disease or any other maternal comorbidity. We aimed to analyse the prevalence of various placental lesions from a 6-months prospective observational study and to correlate the various placental profiles to obstetrical outcome, maternal diseases and pregnancy treatments. The frequency of foetal vascular malperfusion lesion could be estimated at 8.7%, in our population and to understand its neonatal associations. The study groups consisted of 208 consecutive women which ended the pregnancy and have placental analysis during the period of the study. From December 2015 to October 2017, from overall 4398 delivered pregnancies in university obstetrical department, 208 (4.7%) placental analysis have been done and included in the study. The placental analysis have been done for vascular obstetrical complications during the pregnancy (n = 106; 51%), unexplained abnormal foetal heart rate tracings (n = 59; 28,3%), suspicion of intra-amniotic infection (n = 12; 5,7%%), term new-borns Apgar score <7 or arterial cord blood pH ≤ 7 (n = 7; 3,5%), spontaneous preterm delivery (n = 19; 9,1%), intrahepatic cholestasis of pregnancy (n = 5; 2,4%). An adverse obstetrical event was noted in 87 cases (42%): preeclampsia or HELLP syndrome (n = 15; 7%), FGR (n = 59; 28%), gestational diabetes (n = 33; 16%) and gestational hypertension (n = 19; 9%). Placental histological analysis showed abnormal vascular features in 159 cases (76%), inflammatory features in 16 placentas (8%), vascular and inflammatory features in 10 cases (4%), chorioamnionitis in 38 cases (18%) and absence of any abnormality in 43 cases (21%). A cluster analysis of histological features allowed distinguishing three placental patterns: a normal pattern characterised by the absence of any placental lesions, an inflammatory pattern characterised by the presence of villitis and/or chronic intervillositis; a vascular pattern with the presence of thrombosis, maternal floor infarct with massive perivillous fibrin deposition, infarction and chronic villositis hypoxia. Women with inflammatory placental profile have significantly increased frequencies of tobacco use (50% vs. 9%; P = 0.03), pathological vascular Doppler (50% vs. 5%; P = 0.001), FGR (100% vs. 14%; P = 0.0001) and oligohydramnios (67% vs. 5%; P = 0.0001) than those with normal placentas. A higher rate of vascular or inflammatory lesion were observed in women with Hypertensive disorder of pregnancy, where as those with inflammatory pattern have significantly more frequent FGR (100% vs 34%; P = 0.02) and oligohydramnios (67% vs 5%; P = 0.0002). The placenta analysis is important to understand the origin of adverse obstetrical outcome and the risk for subsequent pregnancy.

Morphological, Morphometric, and Histological Evaluation of the Placenta in Cases of Intrauterine Fetal Death.

Background The human placenta is a remarkable organ that develops during pregnancy and is crucial in supporting fetal growth and development. The placenta supplies oxygen and nutrients to the fetus and removes waste products from the fetal bloodstream. It also produces hormones that support pregnancy, such as human chorionic gonadotropin, progesterone, and estrogen. Placental insufficiency occurs when the placenta cannot deliver adequate nutrients and oxygen to the fetus. This can result in intrauterine fetal death (IUFD), stillbirth, intrauterine growth restriction, low birth weight, and premature birth. It can also be associated with developmental delays or long-term health issues for the baby. This study aimed to assess the morphologic, morphometric, and histologic changes in the placenta associated with IUFD and compare it with the placenta of live births. Methodology This study was conducted at the Department of Anatomy in collaboration with the Department of Obstetrics and Gynaecology, Integral Institute of Medical Sciences and Research and King George's Medical University Lucknow, where 60 placentas were studied. Placentas were further categorized into the following two groups: Group A, the study group in which placentas from IUFD were taken (n = 30), and Group B, the control group where placentas from live births were taken (n = 30). Morphological and morphometric features of both groups were recorded and compared. Histological features of placentas from IUFD (Group A) were examined after hematoxylin and eosin staining. Results A total of 60 placentas were observed (Group A and Group B). In Group A (IUFD) and Group B (control group), most pregnancies were multigravidas. Round-shaped placentas were the most common type in both groups (Group A = 46.67%, Group B = 66.67%). The average thickness of placentas from Group A (IUFD) cases was significantly reduced (mean thickness = 1.17 ± 0.07 cm) compared to controls in Group B (mean thickness = 2.04 ± 0.93 cm). The p-value obtained was significant at 0.0001. There was a notable reduction in the average placental diameter in Group A (mean diameter = 241.73 ± 65.54 cm) compared to Group B (mean diameter = 263.72 ± 162.67 cm). The p-value obtained was not significant at 0.49. On histopathological examination of the placentas of Group A (IUFD), perivillous fibrin deposition and high-grade calcification were seen in a significantly high number of placentas (70% and 60%, respectively). Conclusions The knowledge of the placenta's morphologic, morphometric, and histologic changes can be utilized to establish the cause of fetal death. In instances of fetal growth limitation and fetal demise that are clinically inexplicable, they can also explain the causes.

Sonographic Signs of SARS-CoV-2 Placentitis. Association with Pregnancy Outcome.

Being associated with a systemic infection, SARS-CoV-2 affects multiple organs, including the placenta. SARS-CoV-2 placentitis is a new condition that shows the destructive effects of fibrin deposition in the perivillous area, chronic histiocytic intervillositis and trophoblast necrosis after the placenta is infected with SARS-CoV-2. Until now, there have been no published reports regarding the ultrasound signs of massive perivillous fibrin deposition and the recommended monitoring for these cases. Our aim was to analyze the sonographic appearance of the placenta in a series of SARS-CoV-2 infected pregnant women during their third trimester. In all cases included in the present study, we performed serial obstetrical ultrasounds every seven days until delivery, followed by histopathological examination of the placenta postpartum. In women with intrauterine growth restriction (IUGR), sonographic images of the placentas revealed that they matured faster within three weeks of receiving a COVID-19 diagnosis and reached a more rapid senescence. In all cases, there was a gradual increase in placental calcification from week to week, but only in pregnant women with a grade 3 placenta at the moment of inclusion in the study the deterioration was severe, leading to placental insufficiency and subsequently to IUGR. The cases who had an increased placental degree at the time of infection were associated with abnormally rapid placental aging. These aspects can be evaluated sonographically.

Impact of SARS-CoV-2 infection during pregnancy on the placenta and fetus

Pregnant people and their fetuses are vulnerable to adverse health outcomes from coronavirus 2019 disease (COVID-19) due to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been associated with higher rates of maternal mortality, preterm birth, and stillbirth. While SARS-CoV-2 infection of the placenta and vertical transmission is rare, this may be due to the typically longer time interval between maternal infection and testing of the placenta and neonate. Placental injury is evident in cases of SARS-CoV-2-associated stillbirth with massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. Maternal COVID-19 can also polarize fetal immunity, which may have long-term effects on neurodevelopment. Although the COVID-19 pandemic continues to evolve, the impact of emerging SARS-CoV-2 variants on placental and perinatal injury/mortality remains concerning for maternal and perinatal health. Here, we highlight the impact of COVID-19 on the placenta and fetus and remaining knowledge gaps.

Prompt Placental Histopathological and Immunohistochemical Assessment after SARS-CoV-2 Infection during Pregnancy-Our Perspective of a Small Group.

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. This study offers an approach to histopathological and immunohistochemical placental observations from SARS-CoV-2-positive mothers compared to negative ones. Out of the 44 examined placentas, 24 were collected from patients with a SARS-CoV-2 infection during pregnancy and 20 were collected from patients without infection. The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblasts, and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV) and thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p = 0.01) and fibrin deposition (p = 0.01). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%), and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), and chorioamnionitis (5%) and two cases of meconium (19%). Our study sheds light on the changes and differences that occurred in placentas from SARS-CoV-2-infected mothers and the control group. Further research is necessary to definitively establish whether SARS-CoV-2 is the primary culprit behind these intricate complications.

Effects of permanent placental injury due to severe acute respiratory syndrome coronavirus 2 infection during pregnancy on the feto-placental circulation: a cross-sectional study.

The aim of this study was to evaluate the effects of permanent placental injury due to a severe acute respiratory syndrome coronavirus 2 infection during pregnancy on feto-placental circulation. In this cross-sectional study, 83 pregnant women with planned deliveries were divided into two groups according to their severe acute respiratory syndrome coronavirus 2 infection statuses during pregnancy. Their demographic parameters, obstetric histories, and prenatal risks were evaluated. A prenatal fetal Doppler ultrasound examination was performed for all participants, and umbilical artery and middle cerebral artery Doppler parameters were obtained. Postpartum placentas were examined for pathological findings under appropriate conditions. All placentas were evaluated according to the Amsterdam consensus criteria. Mann-Whitney U test, Student's t-test, and chi-square test were used for comparisons. Demographic parameters were statistically similar, except that they were borderline significant for gestational weeks at delivery (p=0.044). In the pathological examination of the placenta, regardless of the trimester of exposure to viral infection, perivillous fibrin deposition and villus dystrophic calcification were more common in group 2 (p=0.016 and p=0.048, respectively) than in group 1. In the prenatal Doppler examination between the groups, no statistically significant difference was found for all of the umbilical artery pulsatile index, middle cerebral artery pulsatile index, and cerebro-placental ratio values. Severe acute respiratory syndrome coronavirus 2 infection during pregnancy causes an increase in perivillous fibrin deposition and villus dystrophic calcification in the placenta. Placental injury caused by the severe acute respiratory syndrome coronavirus 2 virus does not affect fetal Doppler parameters.

Asymptomatic Infant Rib Fractures Are Primarily Non-abuse-Related and Should Not Be Used to Assess Physical Child Abuse.

Finding infant rib fractures was for many years an almost undisputed proof that physical child abuse took place. Yet, these rib fractures are virtually always occult and asymptomatic and are only identified when looked for, usually with X-rays, from physical child abuse accusations related to, e.g., suspicion of the shaken baby syndrome. In a recent systematic literature review (searched in Cochran, Embase, PubMed and Sociological Abstracts), Güvensel questioned the diagnostic accuracy of rib fractures to be caused by abuse, due to lack of sufficient scientific evidence. Further, there is currently a world-wide disagreement between physicians considering themselves child abuse specialized, and physicians that explore non-abuse-related symptoms that may mimic physical abuse, which, it is hoped, will significantly reduce current unjustified child abuse diagnoses. In an attempt to help resolving this disagreement, we hypothesize that the probability of physical child abuse-related infant rib fractures is significantly lower than the probability of all other possible non-abuse-related causes of occult asymptomatic infant rib fractures, e.g., from birth trauma, prematurity, osteogenesis imperfecta, hypermobile Ehlers-Danlos Syndrome, severe chronic placental pathology (e.g., massive perivillous fibrin depositions and severe chronic histiocytic intervillositis), and vitamin-D deficiency. As method, we attempted to assess the incidence of these various causes of infant rib fractures, in the Netherlands and the USA. The results are that the estimated Dutch and USA physical abuse-related infant rib fracture incidences are at least about 250 and 45 times lower than the sum of all the non-abuse-related estimates. Because these latter rib fractures are occult and asymptomatic, it is likely that (many) more could be out there. In conclusion, occult asymptomatic rib fractures develop perinatally, virtually always as birth trauma, in infants with sufficiently weak bones due to vitamin D deficiency, transmitted by their vitamin D deficient pregnant mothers. This group also includes cortical rib cracks due to deformation forces, with an estimated 186/100,000 incidence. And, despite obvious uncertainties in all estimated incidences, we provided strong evidence that our hypothesis has relevance, implying that the abundant occult asymptomatic rib fractures, when found in infants, should not be used to assess potential physical child abuse.

SARS-CoV-2 Infection in Late Pregnancy and Childbirth from the Perspective of Perinatal Pathology.

This review focuses on SARS-CoV-2 infection in placental and fetal tissues. Viremia is rare in infected pregnant women, and the virus is seldom amplified from placental tissues. Definite and probable placental infection requires the demonstration of viral RNA or proteins using in situ hybridization (ISH) and immunohistochemistry (IHC). Small subsets (1.0-7.9%, median 2.8%) of placentas of SARS-CoV-2-positive women showed definite infection accompanied by a characteristic histopathology named SARS-CoV-2 placentitis (SP). The conventionally accepted histopathological criteria for SP include the triad of intervillositis, perivillous fibrin deposition, and trophoblast necrosis. SP was shown to be independent of the clinical severity of the infection, but associated with stillbirth in cases where destructive lesions affecting more than 75% of the placental tissue resulted in placental insufficiency and severe fetal hypoxic-ischemic injury. An association between maternal thrombophilia and SP was shown in a subset of cases, suggesting a synergy of the infection and deficient coagulation cascade as one of the mechanisms of the pathologic accumulation of fibrin in affected placentas. The virus was amplified from fetal tissues in approximately 40% of SP cases, but definite fetal involvement demonstrated using ISH or IHC is exceptionally rare. The placental pathology in SARS-CoV-2-positive women also includes chronic lesions associated with placental malperfusion in the absence of definite or probable placental infection. The direct viral causation of the vascular malperfusion of the placenta in COVID-19 is debatable, and common predispositions (hypertension, diabetes, and obesity) may play a role.

Maternal COVID-19 causing intrauterine foetal demise with microthrombotic placental insufficiency: a case report

BackgroundPregnant 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.CaseHerein 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.ConclusionThis 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.

SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics

Functional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map of placental transcription could provide direct evidence for niche microenvironments with unique functions and transcription profiles. We utilized Visium Spatial Transcriptomics paired with H&E staining to generate 17,927 spatial transcriptomes. By integrating these spatial transcriptomes with 273,944 placental single-cell and single-nuclei transcriptomes, we generated an atlas composed of at least 22 subpopulations in the maternal decidua, fetal chorionic villi, and chorioamniotic membranes. Comparisons of placentae from uninfected healthy controls (n= 4) with COVID-19 asymptomatic (n= 4) and symptomatic (n= 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in syncytiotrophoblasts occurred in both the presence and the absence of maternal clinical disease. With spatial transcriptomics, we found that the limit of detection for SARS-CoV-2 was 1/7,000 cells, and placental niches without detectable viral transcripts were unperturbed. In contrast, niches with high SARS-CoV-2 transcript levels were associated with significant upregulation in pro-inflammatory cytokines and interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), with coordinated shifts in macrophage polarization, histiocytic intervillositis, and perivillous fibrin deposition. Fetal sex differences in gene expression responses to SARS-CoV-2 were limited, with confirmed mapping limited to the maternal decidua in males. High-resolution placental transcriptomics with spatial resolution revealed dynamic responses to SARS-CoV-2 in coordinate microenvironments in the absence and presence of clinically evident disease. This work was supported by the NIH (R01HD091731 and T32-HD098069), NSF (2208903), the Burroughs Welcome Fund and the March of Dimes Preterm Birth Research Initiatives, and a Career Development Award from the American Society of Gene and Cell Therapy.

Investigation of CD56, ADAM17 and FGF21 Expressions in the Placentas of Preeclampsia Cases.

Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.

Histological Properties of Placentas in Acute Herpes Simplex Virus Infection Affecting Genitals

Acute herpes simplex virus infection in pregnant women results in intrauterine infection of the fetus in 45–50% of cases, thus being the cause of septic complications and severe somatic and neurological disorders in the newborn.The aim of the study was to investigate the placentas of new mothers with newly diagnosed herpes simplex virus type 2 infection (HSV-2) using histological and immunochemical methods.Material and methods. This histological study included 10 placentas of new mothers after operative delivery by caesarean section with newly diagnosed HSV-2 infection. The comparison group (control) consisted of 10 placentas of women with a physiological pregnancy. Histological sections of the placenta were stained with hematoxylin and eosin, Giemsa's solution and Picro-Mallory staining. Identification of the pro- and antiinflammatory phenotype of macrophages (CD68, CD163), subpopulations of CD4 and CD8 lymphocytes, TLR4 receptor expression was performed by immunohistochemical method using specific antibodies. Quantification of the cell population and TLR4 receptors was performed morphometrically. The data obtained were statistically analysed using MS Excel (2016) and SPSS Statistics 17.0.Results. Morphological manifestations of acute herpes simplex virus infection were combined inflammatory and compensatory in nature in the third trimester of pregnancy. The histological picture of the fetal part of the placenta demonstrated a decreased number of M2 (antiinflammatory) macrophages and an increased number of M1 (pro-inflammatory) macrophages. The imbalance between CD163+ and CD68+ profiles of placental macrophages with the numerical predominance of the latter evidenced a pronounced cellular immune response; this, in turn, was supported by intense TLR4 immunopositive staining of the fetal part of the placenta. There was perivillous fibrin deposition of varying degrees, villus agglutination, and necrosis of trophoblast cells associated with a relatively small population of CD4+ and CD8+. Villitis of viral etiology was characterized by destructive infiltration of maternal CD8+ T-lymphocytes penetrating the chorionic villi, combined with activated macrophages in the villi of the fetal part of the placenta. Modifications in the proportion of immune cells during HSV-2 infection supported cytotoxic and autoimmune reactions in the placenta in response to HSV-2 introduction.Conclusion. The results obtained evidence the development of a pronounced immunopathological process in the tissues of the fetal part of the placenta, which results in the decreased protective and compensatory properties of the placenta and increases risk of perinatal complications.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Predictive factors for severe placental damage in pregnant women with SARS-CoV-2 infection

IntroductionSARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. MethodsWe retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. ResultsTwelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. DiscussionIn these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes.

Machine learning classification of placental villous infarction, perivillous fibrin deposition, and intervillous thrombus

IntroductionPlacental parenchymal lesions are commonly encountered and carry significant clinical associations. However, they are frequently missed or misclassified by general practice pathologists. Interpretation of pathology slides has emerged as one of the most successful applications of machine learning (ML) in medicine with applications ranging from cancer detection and prognostication to transplant medicine. The goal of this study was to use a whole-slide learning model to identify and classify placental parenchymal lesions including villous infarctions, intervillous thrombi (IVT), and perivillous fibrin deposition (PVFD). MethodsWe generated whole slide images from placental discs examined at our institution with infarct, IVT, PVFD, or no macroscopic lesion. Slides were analyzed as a set of overlapping patches. We extracted feature vectors from each patch using a pretrained convolutional neural network (EfficientNetV2L). We trained a model to assign attention to each vector and used the attentions as weights to produce a pooled feature vector. The pooled vector was classified as normal or 1 of 3 lesions using a fully connected network. Patch attention was plotted to highlight informative areas of the slide. ResultsOverall balanced accuracy in a test set of held-out slides was 0.86 with receiver-operator characteristic areas under the curve of 0.917–0.993. Cases of PVFD were frequently miscalled as normal or infarcts, the latter possibly due to the perivillous fibrin found at the periphery of infarctions. We used attention maps to further understand some errors, including one most likely due to poor tissue fixation and processing. DiscussionWe used a whole-slide learning paradigm to train models to recognize three of the most common placental parenchymal lesions. We used attention maps to gain insight into model function, which differed from intuitive explanations.