Chronic Villitis Research Articles

Decidual Granulomas in Placenta: A unique finding in Preeclamptic Pregnancy

Abstract Introduction/Objective Decidual granulomatous inflammation is a rare finding in the placenta, scarcely reported in the literature. We present an unusual case of a young woman with severe preeclampsia and histological presence of decidual granuloma, involving the placental membranes. Methods/Case Report A 34-year-old female, Gravida 2 Para 1, with prior term vaginal delivery without significant history presented at 26 weeks and 6 days of gestational age with decreased fetal movements. Her home blood pressure was 170 mm of Hg systolic and on presentation, was consistently within the range of <a href=“tel:192- 197/94-97”>192-197/94-97</a> mm of Hg. Biophysical profile of the fetus was 2/10. Complete blood count showed leukocytosis with absolute neutrophilia and urinalysis revealed slight increase in urine protein/creatinine ratio. Clinical diagnosis of severe preeclampsia was made. After initial stabilization, the patient underwent Cesarean section resulting in a premature baby with an uneventful postoperative course. The placenta was sent for histopathological examination. Grossly, the placental disc showed unremarkable membranes with normal appearing fetal and maternal surfaces. Sectioning revealed a central 4.2 cm hemorrhagic area and six tan-white wedge-shaped nodules ranging from 0.8-1.8 cm, occupying approximately 5% and 40% of the maternal surface, respectively. Microscopic examination revealed patchy non-caseating granulomas limited to the decidua, patchy intra-placental hematomas, placental infarcts and chronic villitis. Other findings included scattered avascular villi, villous stromal vascular karyorrhexis, focally increased syncytial knots, and decidual arteriopathy. Gram stain, GMS and acid-fast stains yielded negative results, while immunohistochemical stain CD68 highlighted histiocytes in the granulomas. The final diagnosis of decidual granulomas including the aforementioned microscopic observations was made. Results (if a Case Study enter NA) NA Conclusion Though decidual granulomas are seen in association with infectious and rheumatologic disorders. They can also be observed in severe preeclampsia as in this setting; with unclear underlying pathogenesis, warranting a close follow-up of the newborn and the mother.

Placental chronic inflammatory histopathology and fetal growth in a cohort with universal placental examination

IntroductionChronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both. MethodsComplete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010–August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis. ResultsIn this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight. DiscussionIn summary, CPI lesions’ incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias.

Placental pathology and fetal growth outcomes in pregnancies complicated by maternal obesity.

The rising prevalence of maternal obesity presents a significant health concern because of the possible implications for obstetric complications and neonatal outcomes. Understanding the impact of obesity on placental structure and function as well as fetal growth and infant outcomes is important to improve the care of these potentially high-risk pregnancies. This study aimed to determine the effect of elevated maternal BMI on histopathologic patterns of placental injury and its consequences on fetal growth. Data were collected from an ongoing cohort of maternal-infant dyads in the UCSD Obstetric Registry spanning 2011-2020. Maternal characteristics, including BMI, hypertensive disease and diabetes, placental gross and histopathology, and infant characteristics, including sex and birthweight, were recorded and analyzed. ANOVA and chi-square tests were used in initial analyses, followed by log-binomial and linear regression models adjusted for relevant confounders to determine associations between maternal BMI, specific patterns of placental injury, and infant birthweight percentiles. Among 1366 maternal-infant dyads, placentas from mothers with overweight and obesity were heavier and demonstrated higher adjusted relative risks of chronic villitis (CV), decidual vasculopathy, intervillous thrombosis, and normoblastemia. Placental efficiency, determined by fetal-placental weight ratio, was decreased with increasing BMI. Maternal obesity was associated with higher rates of preterm birth and higher birthweight percentiles. Multiple placental lesions, including maternal (MVM) and fetal vascular malperfusion (FVM), exhibited significant effects on birthweight percentiles; however, only MVM showed a differential effect based on maternal obesity. Presence of obesity in pregnancy is associated with increased rates of placental patterns of injury, decreased placental efficiency, and increased birthweight percentiles. While placental lesions, such as CV, have the potential to negatively impact fetal growth, the resulting birthweight percentiles demonstrate a more complex relationship between maternal obesity and fetal growth, that likely involves placental and fetal adaptation to the altered in utero environment.

COVID-19 and Hypertensive Disorders of Pregnancy: Is the Placenta the Problem? [ID 2683611

INTRODUCTION: The objective of this study is to evaluate the association between COVID-19 infection in pregnancy and placental pathology in order to assess the mechanism of its association with hypertensive disorders of pregnancy (HDP). METHODS: This was a retrospective cohort study that compared placentas of patients who tested positive for COVID-19 during their pregnancy (n=70) to placentas of patients who tested negative for COVID-19 (controls, n=210). Patient demographics, comorbid conditions, and pregnancy complications were obtained from the electronic medical record. RESULTS: Compared with pregnancies negative for COVID-19 infection, maternal COVID-19 infection was not associated with increased incidence of placental pathology including acute funisitis, acute chorioamnionitis, chronic villitis, chorionic pseudocysts, decidual necrosis, Tenney Parker changes, intervillous hemorrhage, infarcts, villous calcifications, meconium-stained amniotic fluid, inflammatory changes, or vascular VTE changes. Based on the logistic regression analysis, after controlling for other variables in the model, the risk of developing HDP was 72.4% higher in patients who tested positive for COVID-19 versus those who did not (odds ratio 1.72; 95% CI [1.09, 2.73]; P=.02). CONCLUSION: Patients who test positive for COVID-19 during pregnancy have an increased risk of HDP. However, there is no association between COVID-19 infection in pregnancy and pathologic findings on placental histology. This suggests that COVID-19 does not exert its effects of increasing the risk of HDP via placental infection or inflammation. Rather, COVID-19 may contribute to the pathogenesis of HDP through cytokine storm, dysregulation of the renin–angiotensin–aldosterone system, or systemic hyperinflammatory response.

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.

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.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium

BackgroundThe Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. ObjectivesWe analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. Study designThe teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. ResultsThe morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. ConclusionThe relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Whole exome sequencing of placental chorangioma

IntroductionPlacental chorangioma is a benign non-trophoblastic vascular proliferation of the placental chorion favored to represent hamartoma-like or hyperplastic capillary lesions. As the exact pathophysiology has not been established, we investigated the molecular characteristics of placental chorangiomas using exploratory whole exome sequencing. MethodsThree cases were retrospectively selected and whole exome sequencing was performed on macrodissected lesions. DNA extraction, DNA quantification, library preparation and sequencing were performed with IDT xGen™ Exome Hybridization Panel v2 for library capture. Sequencing data was analyzed with an in-house bioinformatics pipeline for single-nucleotide variants and insertions/deletions. ResultsAll neonates were delivered at term and had birth weights ranging from 11th-35th percentile for gestational age. All mothers presented with hypertensive disorder during pregnancy. Chorangiomas ranged from 0.7 cm to 5.1 cm and were well-circumscribed near the fetal surface. Case 1 showed a background of chorangiosis and acute subchorionitis, while case 2 had foci of chronic lymphocytic villitis. Whole exome sequencing did not reveal any significant pathologic variants. DiscussionsThe absence of molecular alteration in placental chorangioma is likely indicative of the reactive/non-neoplastic nature of this lesion. The presence of compromised blood flow in the form of hypertensive disorders in our cases may be one of its underlying pathophysiologic mechanisms.

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..

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Histological Alterations in Placentas of Pregnant Women with SARS-CoV-2 Infection: A Single-Center Case Series.

This study aimed to investigate the histopathological changes associated with SARS-CoV-2 infection in placentas. A case series of anatomopathological analysis was conducted on the placentas of pregnant women with SARS-CoV-2 who delivered between March and December 2020 at Santo Amaro Hospital (HSA) in Salvador, Brazil. Out of the 29 placentas examined, the median weight was 423.0 (IQR: 385.0-521.0) g. Among them, 58.3% (n = 14) had inadequate weight relative to the newborn's weight. The histopathological findings revealed that 86.2% (n = 25) of the placentas had poorly defined lobes, and the fetal and maternal surface color was normal in 89.7% (n = 26) and 93.1% (n = 27), respectively. Additionally, 51.7% (n = 15) of the umbilical cords displayed hypercoiling. The most frequent microscopic finding was infarction, present in 35.3% (n = 6) of the cases, followed by 11.8% (n = 2) for each of chorioamnionitis, chronic villitis, focal perivillositis, and laminar necrosis. Analysis of the umbilical cords identified 23.5% (n = 4) cases of intervillous thrombosis, while amnion analysis showed 13.8% (n = 4) cases of squamous metaplasia. Extraplacental membrane examination revealed fibrin deposition in 93.1% (n = 27) of the cases, necrosis in 62.0% (n = 18), calcifications in 51.7% (n = 15), cysts in 37.9% (n = 11), neutrophilic exudate in 17.2% (n = 5), thrombosis in 13.7% (n = 4), and delayed placental maturation in 6.9% (n = 2). All analyzed placentas exhibited histopathological changes, primarily vascular and inflammatory, which indicate SARS-CoV-2 infection in term pregnancies. These alterations could be associated with impaired placental function, fetal growth restriction, preeclampsia, and prematurity. However, further prospective studies are required to validate the type, prevalence, and prognosis of each of these changes.

Chronic choriodeciduitis demonstrates multiple and sex-specific effects on cyto- and chemo-kine levels in newborn dried blood spots while chronic villitis does not.

Chronic choriodeciduitis demonstrates multiple and sex-specific effects on cyto- and chemo-kine levels in newborn dried blood spots while chronic villitis does not.

Placental Syphilis: A Comprehensive Review of Routine Histomorphology, HIV Co-infection, Penicillin Treatment, Immunohistochemistry, and Polymerase Chain Reaction

Introduction: Placental examination is valuable for diagnosing congenital syphilis, but the classic histological triad is not always observed. This study aimed to identify additional morphological clues, evaluate the sensitivity of IHC and qPCR, and investigate the impact of HIV co-infection and penicillin treatment on placental morphology. Materials and methods: Two hundred and fifteen placental specimens with treponemal infection were reviewed. Morphological findings, IHC, and qPCR results were analyzed. Results: Chronic villitis (94%), acute chorioamnionitis (91.6%), and villous immaturity (65.6%) were the most common abnormalities. HIV co-infection and penicillin treatment were associated with reduced frequencies of inflammatory lesions. IHC and qPCR exhibited sensitivities of 74.4 and 25.8%, respectively, confirming the diagnosis in 42 cases with negative or unknown serology. Conclusion: Villitis, chorioamnionitis, and villous immaturity were identified as the predominant placental abnormalities. HIV co-infection and penicillin treatment can impact morphology and hamper the diagnosis. IHC and q-PCR are valuable adjuncts when serology is negative.

Morphological placental findings in women infected with SARS-CoV-2 according to trimester of pregnancy and severity of disease

IntroductionPlacental morphology findings in SARS-CoV-2 infection are considered nonspecific, although the role of trimester and severity of infection are underreported. Therefore, we aimed to investigate abnormal placental morphology, according to these two criteria. MethodsThis is an ancillary analysis of a prospective cohort study of pregnant women with suspected SARS-CoV-2 infection, managed in one maternity, from March 2020 to October 2021. Charting of clinical/obstetric history, trimester and severity of COVID-19 infection, and maternal/perinatal outcomes were done. Placental morphological findings were classified into maternal and fetal circulatory injury and acute/chronic inflammation. We further compared findings with women with suspected disease which tested negative for COVID-19. Diseases’ trimester of infection and clinical severity guided the analysis of confirmed COVID-19 cases. ResultsNinety-one placental discs from 85 women were eligible as a COVID-19 group, and 42 discs from 41 women in negative COVID-19 group. SARS-CoV-2 infection occurred in 68.2% during third trimester, and 6.6% during first; 16.5% were asymptomatic, 61.5% non-severe and 22.0% severe symptomatic (two maternal deaths). Preterm birth occurred in 33.0% (one fetal death). Global maternal vascular malperfusion (MVM) were significant in COVID-19 group whether compared with negative COVID-19 tests group; however, fetal vascular malperfusion lesions and low-grade chronic villitis were not. Three placentas had COVID-19 placentitis. Decidual arteriopathy was associated with infection in first/mid trimester, and chorangiosis in asymptomatic infections. DiscussionPlacental abnormalities after an infection by COVID-19 were more frequent after first/mid-trimester infections. Extensive placental lesions are rare, although they may be more common upon underlying medical conditions.

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

Prepregnancy obesity and risk of placental inflammation at term: a selection bias analysis

Placental histopathology is a resource for investigating obesity-associated pregnancy conditions. However, studies oversample adverse pregnancies, biasing findings. We examine the association between prepregnancy obesity (risk factor for inflammation) and histologic placental inflammation (correlated with impaired infant neurodevelopment) and how selection bias may influence the association. Singleton term deliveries between 2008 and 2012 from the Magee Obstetric Maternal and Infant database were analyzed. Prepregnancy body mass index (BMI) was categorized as underweight, lean (referent), overweight, and obese. Outcomes were diagnoses of acute (acute chorioamnionitis and fetal inflammation) and chronic placental inflammation (chronic villitis). Risk ratios for associations between BMI and placental inflammation were estimated using selection bias approaches: complete case, exclusion of pregnancy complications, multiple imputation, and inverse probability weighting. E-values approximated how susceptible estimates were to residual selection bias. Across methods, obesity was associated with an 8-15% lower risk of acute chorioamnionitis, a 7%-14% lower risk of acute fetal inflammation, and a 12%-30% higher risk of chronic villitis relative to lean women. E-values indicated modest residual selection bias could explain away associations, though few measured indications of placental evaluations met this threshold. Obesity may contribute to placental inflammation, and we highlight robust methods to analyze clinical data susceptible to selection bias.

Placental inflammation and overweight or obesity in term singleton stillbirths in Stockholm County 2002-2018; a case control study.

Stillbirth is a severe pregnancy complication. Maternal obesity is one of the most important modifiable risk factors of stillbirth, yet the biological mechanisms behind this association remain unclear. The adipose tissue is an endocrine organ which, in persons with obesity, causes a hyperinflammatory state. The aim of this study was to investigate inflammation as a contributing mechanism to the risk of stillbirth in women with obesity and if there are possible signs of different BMI phenotypes with different risk. This was a case control study based on all cases of term singleton stillbirth without major fetal malformation in Stockholm County between 2002-2018. Placentas have been examined according to a standardized protocol. Placental inflammatory lesions were compared both between placentas from pregnancies with live born and stillborn infants with different class of body mass index (BMI) as well as among women with stillborn and live born infants with different classes of BMI, respectively. All inflammatory placental lesions were more common in placentas from women with stillbirth compared to placentas from women with live born infants. Vasculitis, funisitis and chronic villitis as well as overall fetal and maternal inflammatory response were present with a significantly increased proportion with increasing BMI in placentas from women with term stillbirth however, there were no differences between placentas from women in different BMI classes with term live born infants. Both acute and chronic inflammatory placental lesions were more common in cases of stillbirth compared to pregnancies with live born infants. There were increased proportions of both acute and chronic placental inflammation (vasculitis, chronic villitis, funisitis and overall fetal and maternal inflammatory response) with increasing BMI among cases with term stillbirth, however no differences among controls with term live born infants.

Development of placental lesions after recovery from COVID-19 during pregnancy: case-control study.

To study whether the occurrence and type of placental lesions vary according to the time of onset of COVID-19 in pregnant women. Case-control study. Departments of Gynaecology-Obstetrics and Pathology, Strasbourg University Hospital, France. Cases were 49 placentas of women with COVID-19. Controls were 50 placentas from women who had a past history of molar pregnancy. COVID-19 placentas were categorised based on whether birth occurred at more or less than 14 days post-infection. Comparison between case and controls. Maternal and neonatal outcomes were recorded. Macroscopic and microscopic examination of the placentas was performed. The rate of vascular complications was higher in the COVID groups than in the controls (8 [16.3%] versus 1 [2%], p = 0.02). Signs of fetal (22[44.9%] versus 13 [26%], p = 0.05) and maternal (44 [89.8%] versus 36 [72.0%], p = 0.02) vascular malperfusion and signs of inflammation (11 [22.4%] versus 3 [6.0%], p = 0.019) were significantly more common in the COVID-19 groups than in the control group. Fetal malperfusion lesions (9 [39.1%] versus 13 [50.0%], p = 0.45) and placental inflammation (4 [17.4%] versus 7 [26.9%], p = 0.42) rates were not significantly different between the two COVID-19 groups. Chronic villitis was significantly more common when the delivery occurred >14 days after infection than in the group that delivered <14 days after infection (7 [26.9%] versus 1 [4.4%], p = 0.05). Our study suggests that SARS-COV-2 induces placental lesions that evolve after disease recovery, especially with the development of inflammatory lesions, such as chronic villitis.

A pregnant with markedly elevated alkaline phosphatase: a case report

Alkaline Phosphatase (ALP) is produced from the liver, kidney, bone and placenta. During pregnancy, ALP may raise markedly with no clear reason. Here, we present a rare case of highly elevated ALP in a 21 years old pregnant woman during the third trimester who had no important past medical history. It was 2800 U/L. Bone, renal, or liver was all normal. Close monitoring of the fetus and his mother until birth was the way of treatment. We had seven weeks postpartum to decline in ALP concentration but did not return to the normal range. The placenta showed lesions of chronic villitis. The extreme incline in ALP during the gestational stages is riskier because the threat here is posed to 2 lives. In such conditions, constant monitoring of ALP in the maternal serum backed with necessary medication is required.

Clinical Features of SARS-CoV-2 Infection During Pregnancy and Associated Placental Pathologies.

We reviewed the clinicopathologic findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed placentas at our institution. We identified patients diagnosed with SARS-CoV-2 during pregnancy (March-October 2020). Clinical data included gestational age at diagnosis and delivery and maternal symptoms. Hematoxylin and eosin slides were reviewed for maternal vascular malperfusion, fetal vascular malperfusion, chronic villitis, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Immunohistochemistry (IHC) for coronavirus spike protein and RNA in situ hybridization (ISH) for SARS-CoV-2 was performed on a subset of blocks. A review of placentas from age-matched patients received March-October 2019 was conducted as a comparison cohort. A total of 151 patients were identified. Placentas in the 2 groups were similar in weight for gestational age and had similar rates of maternal vascular malperfusion, fetal vascular malperfusion, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Chronic villitis was the only significantly different pathologic finding between cases and controls (29% of cases showed chronic villitis vs. 8% of controls, P<0.001). Overall, 146/151 (96.7%) cases were negative for IHC and 129/133 (97%) cases were negative for RNA ISH. There were 4 cases that stained positively for IHC/ISH, 2 of which showed massive perivillous fibrin deposition, inflammation, and decidual arteriopathy. coronavirus disease 2019 (COVID-19)-positive patients were more likely to self-identify as Hispanic and more likely to have public health insurance. Our data suggests SARS-CoV-2 exposed placentas that stain positively for SARS-CoV-2 show abnormal fibrin deposition, inflammatory changes, and decidual arteriopathy. The group of patients with clinical COVID-19 are more likely to show chronic villitis. IHC and ISH evidence of viral infection is rare.