Maternal Vascular Malperfusion Research Articles

Identifying causes and associated factors of stillbirths using autopsy of the fetus and placenta.

The study aimed to evaluate the causes of death and associated factors in cases of stillbirth, using post-mortem examination and applying a rigorous, evidence-based holistic approach. Our retrospective observational study included cases of autopsy following stillbirth that occurred at our tertiary medical center during a period of 8 years. Detailed up-to-date criteria that incorporate clinical reports, medical history, prenatal imaging, and histopathological findings were used to evaluate the cause of death and associated factors. After applying our proposed methodology, 138 cases of stillbirth were classified into eight categories based on the causes of death. A definitive cause of death was observed in 100 (72%) cases, while 38 (28%) cases were considered unexplained. The leading cause of death was placental lesions (n = 39, 28%) with maternal vascular malperfusion (MVM) lesions being the most common (54%). Ascending infection was the second most common cause of fetal death (n = 24, 17%) and was often seen in the setting of preterm labor and cervical insufficiency. The largest category of cause of death was attributed to placental pathology. Using rigorous detailed up-to-date criteria that incorporate pathological and clinical factors may help in objectively classifying the cause of death.

Interdependence of placenta and fetal cardiac development.

The placenta and fetal heart undergo development concurrently during early pregnancy, and, while human studies have reported associations between placental abnormalities and congenital heart disease (CHD), the nature of this relationship remains incompletely understood. Evidence from animal studies suggests a plausible cause and effect connection between placental abnormalities and fetal CHD. Biomechanical models demonstrate the influence of mechanical forces on cardiac development, whereas genetic models highlight the role of confined placental mutations that can cause some forms of CHD. Similar definitive studies in humans are lacking; however, placental pathologies such as maternal and fetal vascular malperfusion and chronic deciduitis are frequently observed in pregnancies complicated by CHD. Moreover, maternal conditions such as diabetes and pre-eclampsia, which affect placental function, are associated with increased risk of CHD in offspring. Bridging the gap between animal models and human studies is crucial to understanding how placental abnormalities may contribute to human fetal CHD. The next steps will require new methodologies and multidisciplinary approaches combining innovative imaging modalities, comprehensive genomic testing, and histopathology. These studies may eventually lead to preventative strategies for some forms of CHD by targeting placental influences on fetal heart development.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report

BackgroundIntrauterine fetal demise is a recognized complication of coronavirus disease 2019 in pregnant women and is associated with histopathological placental lesions. The pathological mechanism and virus-induced immune response in the placenta are not fully understood. A detailed description of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced inflammation in the placenta during fetal demise is crucial for improved clinical management.Case presentationWe report the case of a 27-week gestation SARS-CoV-2-asymptomatic unvaccinated pregnant woman without comorbidities or other risk factors for negative pregnancy outcomes with a diagnosis of intrauterine fetal demise. Histopathological findings corresponded to patterns of subacute inflammation throughout the anatomic compartments of the placenta, showing severe chorioamnionitis, chronic villitis and deciduitis, accompanied by maternal and fetal vascular malperfusion. Our immunohistochemistry results revealed infiltration of CD68+ macrophages, CD56+ Natural Killer cells and scarce CD8+ T cytotoxic lymphocytes at the site of placental inflammation, with the SARS-CoV-2 nucleocapsid located in stromal cells of the chorion and chorionic villi, and in decidual cells.ConclusionThis case describes novel histopathological lesions of inflammation with infiltration of plasma cells, neutrophils, macrophages, and natural killer cells associated with malperfusion in the placenta of a SARS-CoV-2-infected asymptomatic woman with intrauterine fetal demise. A better understanding of the inflammatory effects exerted by SARS-CoV-2 in the placenta will enable strategies for better clinical management of pregnant women unvaccinated for SARS-CoV-2 to avoid fatal fetal outcomes during future transmission waves.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Histopathological and clinical analysis of COVID-19-infected placentas

BackgroundThe impact of COVID-19 pandemic in pregnant patients is an important emerging topic. Evidence of transplacental transmission and typical histopathological alterations in the placenta are controversial in the literature.MethodsThis was a prospective observational cohort multicenter study in which we selected 23 placentas of 21 patients that showed detection of SARS-CoV-2 RNA by RT-PCR in the placenta tissue and described both morphological and clinical characteristics. Immunohistochemistry was performed to localize the virus in the specimens.ResultsMost of the patients were asymptomatic (61.9%) and preterm delivery was observed in 8 patients (34.7%). In relation to histopathological features, all the placentas showed evidence of maternal vascular malperfusion, as well as some degree of villitis with a high frequency of high grade placentitis (73.9%) and chronic and/or acute intervillositis (82.6%). We observed immunopositivity for SARS-CoV-2 antibody in 69.5% of the cases, notably in the syncytiotrophoblast.ConclusionsWe reported histopathological features of placentas with viral detection in the tissue, thus providing evidence that SARS-CoV-2 can affect the placenta, although maternal and neonatal clinical outcome is usually mild.

Chronic villitis as a distinctive feature of placental injury in maternal SARS-CoV-2 infection

BackgroundSARS-CoV-2 infection during pregnancy is associated with increased risk of stillbirth, preeclampsia and preterm birth. However, this does not appear to be due to intrauterine fetal infection, as vertical transmission is rarely reported. There is a paucity of data regarding associated placental SARS-CoV-2 histopathology and their relationship to timing and severity of infection. ObjectiveTo determine if maternal SARS-CoV-2 infection is associated with specific patterns of placental injury and whether these findings differ by gestational age at time of infection or disease severity. Study DesignA retrospective cohort study was performed at University of California San Diego between 03/2020 to 02/2021. Placentas from pregnancies with a positive SARS-CoV-2 test were matched to two sets of controls: one set was time-matched by delivery date and sent to pathology for routine clinical indications, and the other was chosen from a cohort of placentas previously collected for research purposes without clinical indications for pathologic examination prior to the SARS-CoV-2 outbreak. Placental pathologic lesions were defined based on standard criteria and included maternal and fetal vascular malperfusion, and acute and chronic inflammatory lesions. Bivariate analysis was performed with independent Student’s T test and Pearson’s chi-square. Logistic regression was used to control for relevant covariates. Regions of SARS-CoV-2-associated villitis were further investigated using protein-based digital spatial profiling (DSP) assays on the GeoMx platform, validated by immunohistochemistry, and compared to cases of infectious villitis and villitis of unknown etiology. Differential expression analysis was performed to identify protein expression differences between these groups of villitis. ResultsWe included 272 SARS-CoV-2 positive cases, 272 time-matched controls, and 272 historical controls. The mean age of SARS-CoV-2 affected subjects was 30.1 ± 5.5 years and the majority were Hispanic (53.7%) and parous (65.7%). SARS-CoV-2 placentas demonstrated a higher frequency of the four major patterns of placental injury (all p<.001), compared to historical controls. SARS-CoV-2 placentas also showed a higher frequency of chronic villitis (CV) and severe CV (p=.03 for both) compared to time-matched controls, which remained significant after controlling for gestational age at delivery (aOR 1.52, 95% CI 1.01-2.28; aOR 2.12, 95% CI 1.16-3.88, respectively). DSP revealed programmed death-ligand 1 (PD-L1) to be increased in villitis-positive regions of the SARS-CoV-2 (logFC 0.47, adj p-value=0.002) and VUE (logFC 0.58, adj p-value=0.003) cases, but conversely decreased in villitis-positive regions of the infectious villitis group (log FC -1.40, adj p-value<0.001). ConclusionsCV appears to the most specific histopathological finding associated with SARS-CoV-2 maternal infection. CV involves damage to the vasculosyncytial membrane of the chorionic villi, involved in gas/nutrient exchange, suggesting potential mechanisms of placental (and perhaps neonatal) injury, even in the absence of vertical transmission. Surprisingly, changes in protein expression in SARS-CoV-2-associated villitis appear to be more similar to VUE rather than infectious villitis.

Pathogenetic traits of preeclampsia in COVID-19. A relevant literature review

The aim of this study was to present the latest data on the association of preeclampsia and coronavirus infection and on the preeclampsia-like syndrome, and to analyze the current literature on the pathogenetic relationships between COVID-19 and preeclampsia and on morphological changes in placental tissue in patients with these gestational complications.&#x0D; A significant portion of studies indicate an increased risk of developing preeclampsia in patients with coronavirus infection during pregnancy, regardless of gestational age, especially in severe COVID-19, but other researchers report no association between coronavirus infection and the onset of preeclampsia. The supposed pathogenetic connection between these pathologies consists in the development of systemic endothelial dysfunction and dysregulation of the renin-angiotensin-aldosterone system, while the direct effect of SARS-CoV-2 on the placentation is poorly understood and is a subject of debate. A new concept of the so-called “preeclampsia-like syndrome” has been introduced, which presumably occurs in patients with a severe form of the novel coronavirus infection as its extrapulmonary manifestation. The measurement of the ratio of soluble fms-like tyrosine kinase-1 activity to the level of placental growth factor ratio has been proposed as a differential diagnostic test between preeclampsia and the preeclampsia-like syndrome, but its prognostic value remains ambiguous. The morphological examination of placentas in patients with coronavirus infection and preeclampsia indicates the signs of maternal and fetal vascular malperfusion.&#x0D; The literature on the association between coronavirus infection and preeclampsia remains controversial, however, the better half of the researchers is indicative of a significant increase in the risk of developing this serious complication in pregnant women with COVID-19, especially for its severe form. New information about the preeclampsia-like syndrome, as well as the virtual absence of studies of placental morphology in patients with preeclampsia and coronavirus infection during pregnancy, dictate the need for further study to better understand the association between these two pathologies, determine the possibilities of patient surveillance and prevent complications.

Angiogenic imbalance in pregnancies with preterm prelabor rupture of membranes between 34 and 37 weeks of gestation.

This study aimed to identify whether microbial invasion of the amniotic cavity and/or intra-amniotic inflammation in women with late preterm prelabor rupture of membranes (PPROM) was associated with changes in concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and its ratio in maternal serum, and whether placental features consistent with maternal vascular malperfusion further affect their concentrations. This historical study included 154 women with singleton pregnancies complicated by PPROM between gestational ages 34+0 and 36+6 weeks. Transabdominal amniocentesis was performed as part of standard clinical management to evaluate the intra-amniotic environment. Women were categorized into two subgroups based on the presence of microorganisms and/or their nucleic acids in amniotic fluid (determined by culturing and molecular biology method) and intra-amniotic inflammation (by amniotic fluid interleukin-6 concentration evaluation): (1) those with the presence of microorganisms and/or inflammation (at least one present) and (2) those with negative amniotic fluid for infection/inflammation (absence of both). Concentrations of sFlt-1 and PlGF were assessed using the Elecsys® sFlt-1 and Elecsys® PlGF immunoassays and converted into multiples of medians. Women with the presence of microorganisms and/or inflammation in amniotic fluid had lower serum concentrations of sFlt-1 and sFlt-1/PlGF ratios and higher concentrations of PlGF compared with those with negative amniotic fluid. (sFlt-1: presence: median 1.0 multiples of the median (MoM), vs negative: median: 1.5 MoM, P = 0.003; PlGF: presence: median 0.7 MoM, versus negative: median 0.4 MoM, P = 0.02; sFlt-1/PlGF: presence: median 8.9 vs negative 25.0, P = 0.001). Higher serum concentrations of sFlt-1 and sFlt-1/PlGF ratios as well as lower concentrations of PlGF were found in the subsets of women with maternal vascular malperfusion than in those without maternal vascular malperfusion. Among women experiencing late PPROM, angiogenic imbalance in maternal serum is primarily observed in those without both microbial invasion of the amniotic cavity and intra-amniotic inflammation. Additionally, there is an association between angiogenic imbalance and the presence of maternal vascular malperfusion.

Sickle cell disease and increased adverse maternal and perinatal outcomes in different genotypes

BackgroundSickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established. MethodsA retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sβ) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available. ResultsSixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sβ (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sβ (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings ConclusionSCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

Impact of COVID-19 disease on placental histopathology. PLAXAVID study.

The impact of COVID-19 on pregnancy has been analyzed suggesting an increased risk of placental lesions that might lead to maternal and neonatal complications. However, the current published evidence is not conclusive because contradictory results. PLAXAVID is an observational, retrospective, histopathological, single-center study that aimed to evaluate the prevalence of vascular and inflammatory lesions in placental and umbilical cord samples of one hundred women infected by SARS-CoV-2 during pregnancy. The histopathological analysis showed that in most of the placentas (77.8%) there were signs of maternal vascular malperfusion (MVM; primary endpoint). The most common MVM features were an accelerated villous maturation (37.4%), central villous infarcts (33.3%), and villous agglutination (46.5%). Fetal vascular malperfusion (FVM) was identified in 57.6% of samples, and the most frequent features were hyalinized avascular villi (38.4%), fetal vascular thrombi (20.2%) and umbilical cord at risk of partial obstruction (14.1%). Acute and chronic inflammatory pathology were noticed in 22.2% and 49.5% of placentas, respectively. No significant correlations were found between MVM presence and the time, duration, and severity of infection, nor with the duration of pregnancy. However, in critically ill patients, the pregnancy duration (p=0.008), newborn weight (p=0.003), and APGAR test scores (p<0.001) were significantly lower. The same trend was observed considering the presence of infection at the time of delivery and in preterm births. A very high percentage of placentas with vascular and/or inflammatory lesions was found in the analyzed cohort. Therefore, PLAXAVID study results supported that COVID-19 should be considered a risk factor during gestation and requires close monitoring of pregnancy.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

Insights into Placental Pathology: Analyzing Patterns and Fetal Outcomes in 205 Livebirths at Bugando Medical Centre, Mwanza, Tanzania

Background: The placenta facilitates vital nutrient exchange between fetus and mother, offering insights into fetal and maternal health. Despite its significance, research on placental histopathology in Tanzania is scarce. This study investigates placental features, maternal factors, and their impact on fetal outcomes at Bugando Medical Centre from January to May 2022. Methods: This 5-month cohort study included 205 mothers delivering at BMC. Fetal outcomes were evaluated at birth and after seven days, with maternal characteristics recorded at delivery. Participants were from the twenty-eighth week of gestation, excluding those with intrauterine fetal death or multiple pregnancies. Data on placental histology, maternal factors, and fetal outcomes were collected systematically, while statistical analysis employed STATA version 15, utilizing descriptive statistics. Results: In this study of 205 placentas, participants had a median age of 29 years and a mean gestational age of 38 weeks. Histopathological patterns were present in 61% of placentas, with acute inflammation (22%) and maternal vascular malperfusion (20.8%) being most common. Favorable outcomes were observed in 81% of newborns, while 19% experienced poor outcomes, including 1.9% early neonatal deaths. Most placental lesions were mild (53.6%), with severe pathology in 2.9% of cases. Acute inflammation correlated with various admission reasons, especially neonatal sepsis (60%). Maternal vascular lesions were associated with prematurity (63.6%) and birth asphyxia (40%). Chronic inflammation was more prevalent among low-birth-weight infants (18.8%), while very low birth weight was common in cases of maternal vascular lesions (68.8%). Conclusion: The majority of placentas showed normal or mild pathology, associated with positive fetal outcomes. Further research is needed to understand placental changes and their impact on maternal-fetal health.

Non-hypertensive gestational diabetes mellitus: Placental histomorphology and its association with perinatal outcomes

IntroductionGestational diabetes mellitus (GDM) exerts a great impact on the placenta and reflects changes on placentas both morphological and functionally. The aims of this study are to evaluate the prevalence of placental histopathological lesions in pregnancies complicated by GDM compared to gestational age-matched controls, and their association with maternal and fetal complications. MethodsFifty-four singleton GDM-complicated pregnancies were recruited and compared to 33 consecutive normal pregnancies. Two pathologists, blinded to all clinical data, reviewed and evaluated all histological samples of the placentas in accordance with Amsterdam criteria. Relevant demographic, clinical data and primary birth outcomes were recorded. ResultsA myriad of histomorphological abnormalities, including chronic inflammation (n = 9/54, p = 0.031), histological chorioamnionitis (n = 23/54, p < 0.001), umbilical/chorionic vasculitis (n = 9/54, p = 0.031), changes related to maternal vascular malperfusion (n = 22/54, p = 0.003), chorangiosis (n = 10/54, p = 0.046) and villous dysmaturity (n = 9/54, p = 0.012) were observed more frequently in the GDM placentas compared to the controls. Additionally, GDM significantly increased the risk of fetal complications, including macrosomia/fetal growth restriction (n = 13/54, p = 0.004). DiscussionHistoarchitectural abnormalities were observed more frequently in placentas of GDM pregnancies compared to the controls. Our findings support the hypothesis that diabetic-induced damage in the placental function may be associated with the increased in fetal growth disorders in GDM-complicated pregnancies.

A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia

Objective Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. Methods This retrospective case–control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. Results 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924–2926) pg/mL vs. 630 (448–4002) pg/mL, p = .026, and late preeclampsia: 1833 (1441–5534) pg/mL vs. 910 (526–6178) pg/mL, p = .021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070–3188) pg/mL vs. without MVM: 888 (812–1781) pg/mL, p = .03; and with MVM vs. control: 630 (448–4002) pg/mL, p = .04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p = .3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392–3135) pg/mL vs. control: 910 (526–6178), p = .045; and without MVM: 2023 (1578–8936) pg/mL vs. control, p = .01]. Conclusions MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.

Histopathological Changes and Clinical Outcomes in Placentas of COVID-19 Positive Mothers: A Cohort Study

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 &lt;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.

973 Placental gene expression: histologic evidence of maternal vascular malperfusion and small for gestational age newborns

973 Placental gene expression: histologic evidence of maternal vascular malperfusion and small for gestational age newborns

Comparison of placental pathologies in pregnant women with COVID-19 according to disease severity

Aims: To evaluate the placental pathologies of pregnant women diagnosed with COVID-19 according to disease severity. &#x0D; Materials and method: This retrospective study was conducted at a tertiary center between April 2020 and February 2023. The placentas of 125 pregnant women in their third trimester who were positive for SARS-CoV-2 were examined. Placental pathologies were classified according to the modified Amsterdam criteria. According to the disease severity, the patients were divided into two groups: non-severe COVID-19 (n=104) and severe COVID-19 (n=21). Placental pathology results were compared between the two groups. &#x0D; Results: The rates of maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM) were 90.4% and 45.2% in the non-severe COVID-19 group. Whereas it was significantly lower at 71.4% and 19% in the severe COVID-19 group (p=0.018 and p=0.026, respectively). The rate of delayed villous maturation (DVM) was 9.5% in the severe COVID-19 group and 1% in the non-severe COVID-19 group, indicating a statistically significant difference (p=0.019). Inflammatory pathologies and other pathological findings were similar between the two groups. Intensive care unit (ICU) admission, presence of accompanying maternal diseases, and postpartum complications were statistically significantly higher in the severe COVID-19 group (p

Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis.

To evaluate maternal risk factors associated with chronic villitis of unknown etiology (VUE) and to describe cooccurring placental pathologies. A retrospective case-control study was conducted using placental pathology records from deliveries ≥ 20 weeks between 2010 and 2018. Cases were placentas with documented chronic villitis without infectious cause, hereafter called VUE. Controls were placentas without this diagnosis, matched to the cases 2:1. Maternal and neonatal demographic and clinical data were collected. Descriptive statistics are reported with Fisher's exact test or a chi-squared test, as appropriate, and multivariable conditional logistic regression was conducted. Our study included 352 cases with VUE and 657 controls. A diagnosis of gestational diabetes (p = 0.03) and gestational hypertension (p = 0.06) was 1.5 times more likely to occur in those with a VUE diagnosis. A trend was also seen for chronic hypertension (odds ratio [OR] = 1.7, p = 0.07) and preeclampsia (OR = 1.5, p = 0.09) compared with controls. Placentas with VUE, specifically high-grade VUE, were more likely to be small for gestational age (p = 0.01), and to be diagnosed with other placental findings including lymphoplasmacytic or chronic deciduitis (p < 0.01), maternal (p < 0.01) and fetal vascular malperfusion (p = 0.02), and chorionitis (acute or chronic; p < 0.01). Gestational diabetes and hypertension were associated with a diagnosis of VUE, and overall, VUE placentas have more abnormal placental findings compared with control. Understanding VUE risk factors may facilitate prenatal care strategies and counseling to achieve the best outcomes for pregnant patients and their neonates. · VUE is a common inflammatory lesion of the placenta.. · Gestational diabetes and hypertension are associated with a VUE diagnosis.. · Findings of other placental pathologies increase in VUE..

Automated detection of microscopic placental features indicative of maternal vascular malperfusion using machine learning

IntroductionHypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR) are common obstetrical complications, often with pathological features of maternal vascular malperfusion (MVM) in the placenta. Currently, clinical placental pathology methods involve a manual visual examination of histology sections, a practice that can be resource-intensive and demonstrates moderate-to-poor inter-pathologist agreement on diagnostic outcomes, dependant on the degree of pathologist sub-specialty training. MethodsThis study aims to apply machine learning (ML) feature extraction methods to classify digital images of placental histopathology specimens, collected from cases of HDP [pregnancy induced hypertension (PIH), preeclampsia (PE), PE + FGR], normotensive FGR, and healthy pregnancies, according to the presence or absence of MVM lesions. 159 digital images were captured from histological placental specimens, manually scored for MVM lesions (MVM- or MVM+) and used to develop a support vector machine (SVM) classifier model, using features extracted from pre-trained ResNet18. The model was trained with data augmentation and shuffling, with the performance assessed for patch-level and image-level classification through measurements of accuracy, precision, and recall using confusion matrices. ResultsThe SVM model demonstrated accuracies of 70 % and 79 % for patch-level and image-level MVM classification, respectively, with poorest performance observed on images with borderline MVM presence, as determined through post hoc observation. DiscussionThe results are promising for the integration of ML methods into the placental histopathological examination process. Using this study as a proof-of-concept will lead our group and others to carry ML models further in placental histopathology.

Outcome-Based Risk Stratification Model for the Diagnosis of Placental Maternal Vascular Malperfusion

The Amsterdam Consensus Statement introduced the term maternal vascular malperfusion (MVM) to group a constellation of findings associated with impaired maternal–placental circulation. In isolation, these findings are relatively common in placentas from normal gestations, and there is uncertainty on how many, and which, are required. We aimed to determine the criteria essential for MVM diagnosis in correlation with obstetrical outcomes. A total of 200 placentas (100 with a reported diagnosis of MVM and 100 controls matched by maternal age and gravida-para-abortus status) were reviewed to document MVM features. Obstetrical outcomes in the current pregnancy were recorded including hypertension, pre-eclampsia with or without severe features, gestational diabetes, prematurity, fetal growth restriction, and intrauterine fetal demise. On univariate logistic regression analysis, adverse outcome was associated with low placental weight (LPW, <10% percentile for gestational age), accelerated villous maturation (AVM), decidual arteriopathy (DA), infarcts (presence and volume), distal villous hypoplasia, and excess multinucleated trophoblast in basal plate ≥2 mm (all P < .01) but not with retroplacental hemorrhage. In a multivariable model DA, infarcts and AVM were significantly associated with adverse outcomes, whereas LPW showed a trend toward significance. A receiver–operating characteristic curve including these 4 parameters showed good predictive ability (area under the curve [AUC], 0.8256). Based on the probability of an adverse outcome, we recommend consistent reporting of DA, AVM, infarcts, and LPW, summarizing them as “diagnostic of MVM” (DA or AVM plus any other feature, yielding a probability of 65%–97% for adverse obstetrical outcomes) or “suggestive of MVM” (if only 1 feature is present, or only 2 features are infarcts plus LPW, yielding a probability of up to 52%). Other features such as distal villous hypoplasia, excess (≥2 mm) multinucleated trophoblast, and retroplacental hemorrhage can also be reported, and their role in MVM diagnosis should be further studied.