Chronic Villitis Of Unknown Etiology Research Articles

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.

Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis - A new link to a rare placental lesion?

IntroductionMaternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation. Material and methodsIn a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations. ResultsChronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p ​= ​0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. DiscussionPlacentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.

Chronic villitis of unknown etiology: Investigations into viral pathogenesis

IntroductionChronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response. MethodsWe extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta. ResultsWe detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE. DiscussionThese data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.

M1 macrophages involved in the pathogenesis of placental chronic villitis of unknown etiology

Introduction Placental villitis is characterized by the presence of inflammatory infiltrate in the placental villous. The objective of this study was to characterize in villitis of unknown etiology (VUE) of the human placentas the subpopulation of M1, important effector cells, and M2 macrophages, immunoregulatory cells. Methods Sixteen cases of VUE and three control placentas were examined using immunohistochemistry with antibodies for CD3, CD68, CD11c, and CD163. Results CD11c appeared predominantly in the inflamed villi when compared to the normal areas (p<.001). These cells corresponded to 41.2% of the macrophage population in the inflamed area and were mainly present inside the villi (36%). With regards to CD163, these cells tended to be in higher amounts in the inflamed villi when compared to CD11c and normal areas. Discussion We conclude that the almost exclusive presence of M1 macrophages in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The greater amount of M2 in villitis and normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

Maternal-Fetal Inflammation in the Placenta and the Developmental Origins of Health and Disease.

Events in fetal life impact long-term health outcomes. The placenta is the first organ to form and is the site of juxtaposition between the maternal and fetal circulations. Most diseases of pregnancy are caused by, impact, or are reflected in the placenta. The purpose of this review is to describe the main inflammatory processes in the placenta, discuss their immunology, and relate their short- and long-term disease associations. Acute placental inflammation (API), including maternal and fetal inflammatory responses corresponds to the clinical diagnosis of chorioamnionitis and is associated with respiratory and neurodevelopmental diseases. The chronic placental inflammatory pathologies (CPI), include chronic villitis of unknown etiology, chronic deciduitis, chronic chorionitis, eosinophilic T-cell vasculitis, and chronic histiocytic intervillositis. These diseases are less-well studied, but have complex immunology and show mechanistic impacts on the fetal immune system. Overall, much work remains to be done in describing the long-term impacts of placental inflammation on offspring health.

Correlation of Placental Magnetic Resonance Imaging With Histopathologic Diagnosis: Detection of Aberrations in Structure and Water Diffusivity.

Noninvasive methods to identify placental pathologic conditions are being sought in order to recognize these conditions at an earlier stage leading to improved clinical interventions and perinatal outcomes. The objective of this study was to examine fixed tissue slices of placenta by T2- and diffusion-weighted magnetic resonance imaging (MRI) and correlate the images with placental pathologic findings defined by routine gross and histologic examination. Four formalin-fixed placentas with significant placental pathology (maternal vascular malperfusion, chronic villitis of unknown etiology, and massive perivillous fibrin deposition) and 2 histologically normal placentas were evaluated by high-resolution MRI. Representative placental slices were selected (2 cm long and 10 mm wide) and rehydrated. Imaging was performed on a Bruker Avance 14.1 T microimager. Diffusion-weighted images were acquired from 16 slices using slice thickness 0.5 mm and in-plane resolution approximately 100 µm × 100 µm. T2 maps were obtained from the same slices. T2 relaxation time and apparent diffusion coefficient (ADC) were acquired from representative regions of interest and compared between normal and diseased placentas. In T2- and diffusion-weighted images, the placental microstructure differed subjectively between diseased and normal placentas. Furthermore, diseased placentas showed statistically significantly longer mean T2 relaxation times and generally higher mean ADC. Diffusion- and T2-weighted MRI can potentially be used to detect significant placental pathology by using T2 relaxation time and ADC as markers of altered placental microstructure.

Seasonal Variation of Chronic Villitis of Unknown Etiology.

Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of the placenta. VUE is hypothesized to result from an alloimmune response or as response to an unidentified infection. Lack of a seasonal trend is thought to support VUE as an alloimmune response, though data on seasonal VUE trends are limited. Data were obtained from a hospital in Chicago, Illinois, from 2011-2016. Placentas sent to pathology were reviewed using a standardized protocol, and VUE cases were identified based on an automated text search of pathology records. We used monthly VUE prevalence estimates to investigate the annual trend, and we used Poisson regression to evaluate seasonal variation in the number of VUE cases. There were 79 825 deliveries within the study period. Pathologists evaluated 12 074 placentas and identified 2873 cases of VUE. Regression results indicate that the risk of VUE is 16% to 17% higher in the fall and winter as compared to the summer (fall relative risk [RR]: 1.17, 95% confidence interval [CI]: 1.06-1.29; winter RR: 1.16, 95% CI: 1.05-1.29). Our results suggest that there may be seasonal variation in VUE prevalence, particularly for low-grade VUE. Future studies should evaluate seasonal variation in a representative sample rather than relying on pathology reports to estimate prevalence.

Histological Features of Shallow Placental Implantation Unify Early-Onset and Late-Onset Preeclampsia

Preeclampsia is distinguishable from other hypertensive conditions of pregnancy by its high rates of decidual arteriopathy, the uterine type of chronic hypoxic placental injury, the occurrence of villous infarctions, and clusters of multinucleate trophoblasts in the maternal floor. To retrospectively study the clinical and placental phenotypes of 230 women with early-onset preeclampsia, 261 women with late-onset preeclampsia, and 5059 women without hypertension in pregnancy (comparative group), 24 clinical and 46 placental phenotypes were statistically compared (analysis of variance, χ2 with Bonferroni correction). The frequency of decidual arteriopathy (both hypertrophic and atherosis), patterns of chronic hypoxic placental injury, villous infarction, membrane laminar necrosis, membrane microscopic chorionic pseudocysts, clusters of maternal floor multinucleated trophoblasts, excessive number of extravillous trophoblasts, and intervillous thrombi was strikingly higher in both late-onset preeclampsia and early-onset preeclampsia than in the comparative group without hypertension in pregnancy. All 3 patterns of chronic hypoxic placental injury were 2- to 3-fold more common in preeclampsia. Although the preuterine pattern was as common in early-onset preeclampsia as it was in late-onset preeclampsia, the postuterine pattern was 2-fold more common in early-onset preeclampsia, and chronic villitis of unknown etiology was more common in late-onset preeclampsia than in the other 2 groups. Features of shallow placental implantation occurred at the same frequency in early-onset preeclampsia as in late-onset preeclampsia, which reflects an underlying common pathological mechanism in both subgroups of preeclampsia, while hypoxic lesions and patterns of placental injury were more common in early-onset preeclampsia than in late-onset preeclampsia, which correlates with more severe clinical outcomes of the former.

Evaluation of Pattern of Immunostaining for Immunoglobulins and Complement Factors in Placentas with Chronic Villitis of Unknown Etiology: A Pilot Study

Evaluation of Pattern of Immunostaining for Immunoglobulins and Complement Factors in Placentas with Chronic Villitis of Unknown Etiology: A Pilot Study

Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level expression and demonstrate that IgJ expression was largely attributable to the presence of plasma cells as part of chronic deciduitis and that IgA positive plasma cells are associated with chronic deciduitis occurring in combination with chronic chorioamnionitis and chronic villitis of unknown etiology but not with isolated chronic deciduitis.

Chronic villitis of unknown etiology and massive chronic intervillositis have similar immune cell composition

IntroductionChronic villitis of unknown etiology (CVUE) and massive chronic intervillositis (MCI) are placental lesions associated with infiltration of mononuclear cells in the chorionic villi and the intervillous spaces, respectively. It is not well known whether immune cells in CVUE and MCI have similar phenotypic characteristics. MethodsA cross-sectional study of third trimester placentas was conducted to identify immune cell subpopulations in CVUE and MCI (n = 17/group). CVUE was diagnosed with H&E staining and antibody to CD3 in serial sections; and MCI, by the presence of massive infiltration of mononuclear cells in the intervillous spaces. Immune cells, ICAM-1 expression and nuclear factor κB (NF-κB) activation were determined immunohistochemically. ResultsCVUE and MCI showed similar infiltrates, mainly CD68+ and CD3+ cells. Most cells (>80%) were CD45RB+, and one third were CD45RO+ in both lesions. There were slightly more CD8+ than CD4+ cells in both CVUE and MCI. More than 90% of cells in CVUE and MCI were ICAM-1+ with NFκB nuclear localization. Syncytiotrophoblast ICAM-1 expression was significantly (p < 0.001) higher in MCI (mean of 81.0; range of 71.6–86.0) than in CVUE (52.4; 36.4–59.4) or normal placentas (0.2; 0.0–0.6). Both, failure of physiologic transformation of spiral arteries and placental atherosclerosis-like lesions of atherosis were significantly more frequent in MCI than in CVUE or normal placentas (p = 0.044 and p = 0.007, respectively). DiscussionThese finding suggest that MCI and CVUE have very similar infiltration of immune cells although MCI has more severe placental lesions.

Positive C4d Immunostaining of Placental Villous Syncytiotrophoblasts Supports Host-Versus-Graft Rejection in Villitis of Unknown Etiology

ABSTRACT Chronic villitis of unknown etiology (VUE) occurs in 5% of placentas submitted to pathology and is characterized by lymphohistiocytic infiltration of chorionic villi. VUE is associated with fetal growth restriction, preterm birth, and recurrent pregnancy loss. Accumulating evidence indicates that VUE may represent a host-versus-graft reaction analogous to transplant rejection. Pathologists routinely screen for antibody-mediated rejection in transplant biopsies by immunostaining for C4d, which highlights the recognition of donor cells by the host immune system. Since the hemochorial placenta is bathed in maternal blood, we hypothesized that cases of VUE may show C4d deposition onto villous syncytiotrophoblasts (STB). Chronic villitis was diagnosed in 82 of 1986 (4%) singleton placentas submitted to our department from 2007 through 2011. Forty randomly selected cases were gestational age-matched with 40 negative controls. Patient charts were reviewed and representative placental sections were immunostained for C4d. A positive C4d result was defined as circumferential immunostaining of the STB around at least one villous, or strong staining of fetal endothelial cells in the chorionic plate or stem villi. Our data indicate that VUE usually occurs in the 3rd trimester (37 ± 0.5 weeks) and is associated with significantly reduced placental weight (P = 0.006). Positive C4d staining of STB was more common in VUE (35/40, 88%) compared with negative controls (2/40, 5%) (P < 0.0001). It was also more common in multiparous (35/66, 53%) than primiparous (2/14, 14%) women (P < 0.01). Although the precise mechanism remains to be determined, our data support the hypothesis that VUE may represent host-versus-graft rejection by the mother.

Immunohistochemical Analysis Reveals an Influx of Regulatory T Cells and Focal Trophoblastic STAT-1 Phosphorylation in Chronic Villitis of Unknown Etiology

Maternal T cells and fetal macrophages constitute the primary infiltrate of chronic villitis of unknown etiology (CVUE), but the role of CD25(+)/FOXP3(+) regulatory T (Treg) cells in CVUE has not been examined. Moreover, little is known about the expression of immune markers, such as the major histocompatibility complex (MHC) class II antigen, human leukocyte antigen-DR (HLA-DR), in trophoblasts in this disease. We, therefore, examined CVUE placentas for the presence of Treg cells and aberrant activation of HLA-DR in trophoblasts. Sequential formalin-fixed, paraffin-embedded tissue sections from 8 CVUE placentas and 10 control placentas were stained by immunohistochemistry with antibodies for CD3, CD4, CD8, CD20, CD25, FOXP3, CD56, CD68, HLA-DR, STAT-1, and phosphorylated STAT-1 [P-(Y701)-STAT-1]. T cells and histiocytes were confirmed as the inflammatory infiltrate in CVUE. In areas of CVUE, histiocytes strongly expressed HLA-DR and nuclear P-(Y701)-STAT-1, and the relative numbers of CD25(+)/FOXP3(+) Treg cells were increased, compared with control placentas. In 5 of 8 CVUE cases, there was patchy nuclear expression of P-(Y701)-STAT-1 in syncytiotrophoblast most extensively involved by villitis, but no other marker examined was detected in the trophoblast cell layer. We confirmed the influx of T cells and histiocytes in CVUE. Our results are the 1st, to our knowledge, to identify increased numbers of Treg cells in CVUE vs noninflamed placentas. However, we were unable to verify HLA-DR expression in trophoblasts of placentas with CVUE, suggesting that this does not contribute to the influx of T cells. Our observation that P-(Y701)-STAT-1 expression in a syncytiotrophoblast is restricted to regions of inflammation suggests that the JAK-STAT-1 pathway is aberrantly activated in these cells.

Association des corticoïdes à l’aspirine pour la prévention des récidives de villite ou d’intervillite chroniques d’étiologie indéterminée

We report the cases of two patients who had a favorable outcome with aspirin and corticosteroid therapy during pregnancy for chronic villitis of unknown etiology complicated by labor asphyxia and further intrauterine fetal demise in one gravida 3 patient and for chronic intervillositis of unknown etiology diagnosed after three perinatal deaths in another patient (gravida 4). Chronic villitis of unknown etiology (CVUE) is detected in 7 to 33% of placentas, mainly after intrauterine growth retardation (IUGR), unexplained prematurity, preeclampsia, perinatal asphyxia and intrauterine fetal death (IUFD). The less frequent chronic intervillositis of unknown etiology (CIUE) (0.6 to 0.9/1.000) has been implicated in recurrent severe pregnancy complications, such as spontaneous abortions, IUGR and IUFD. Histopathology and immunohistology are in favor of an immune response against the foreign fetal allograft. The favorable results obtained with corticosteroids and aspirin remain to be confirmed by larger series.

Chronic chorioamnionitis: A clinicopathologic and immunohistochemical study

Lymphocytic inflammation of the fetal membranes is unusual and has been termed chronic chorioamnionitis. We report the clinicopathologic and immunohistochemical findings in 31 placentas with chronic chorioamnionitis. The most common histopathologic association was chronic villitis of unknown etiology, which was identified in 22 (71%) of the 31 placentas. The severity of the chronic villitis did not correlate with the severity of chronic chorioamnionitis. Additional placental findings included chronic interviilositis in two, fetal vessel thrombosis in five, hemorrhagic endovasculitis in four, decidual chronic vasculitis in three, and atherosis in one. Maternal history included pregnancy-induced hypertension in six and diabetes in one. Twelve infants were preterm, and five had intrauterine growth retardation. There was no neonatal sepsis or death. Immunohistochemical staining in areas of chronic chorioamnionitis showed CD3+ and CD8+ cells present in moderate numbers, and CD4+ cells in smaller numbers. CD20+ and CD56+ cells were rare or absent. Chronic chorioa mnionitis is commonly associated with chronic villitis of unknown etiology, shares similar clinical associations, and may have a related cause, possibly immunologic.

Risk factors for recurrence of hemorrhagic endovasculitis of the placenta

To assess the potential for recurrence of placental hemorrhagic endovasculitis and to identify clinical or pathologic cofactors that might influence recurrence of this lesion or subsequent pregnancy outcome. Ninety-seven women with a placenta affected by hemorrhagic endovasculitis, who also had at least one placenta referred to the Michigan Placental Tissue Registry from a subsequent pregnancy, were identified from 10,531 referrals between 1978 and 1988. Histologic slides from 209 placentas and clinical data from 211 infants (two sets of twins) from initial (first) and subsequent referrals were analyzed. Placentas were graded for the presence, extent, and severity of hemorrhagic endovasculitis and chronic villitis of unknown etiology; for placental lesions indicative of hypertensive maternal vessel disease; and for intravascular nucleated erythrocytes and chorionic thrombi. Maternal data included age, gravidity, number of previous losses, and history of toxemia or hypertension. All data were analyzed for significance using chi2 and t tests. Outcome assessment was based on recurrence of hemorrhagic endovasculitis and infant viability with the second referral. With first referrals, 80 of 98 infants (81.6%) were stillborn. Among second referrals, 26 of 98 infants (26.5%) were stillborn. Hemorrhagic endovasculitis recurred in 28 second placentas (28.9%); of these, 18 infants (64.3%) were stillborn. Higher rates of recurrence were found with progressively higher first-referral chronic villitis severity scores (P < .02), higher hypertensive placental lesion scores (P < .001), and first referrals with a history of toxemia or hypertension (P < .02). Recurrence of hemorrhagic endovasculitis was higher in patients with two or more of these factors in first referrals (P < .001). Subsequent stillbirth was more frequent with progressively higher first-referral hypertensive placental lesion scores (P < .01) and in first placentas with two or more risk factors (P = .064). Hemorrhagic endovasculitis severity scores, intravascular nucleated erythrocytes, and chorionic thrombi were associated with stillbirth in index pregnancies only. Maternal age, gravidity, or history of prior losses were not predictive. Placental hemorrhagic endovasculitis is associated with pregnancy loss and can recur in some patients. Interrelations among placental hemorrhagic endovasculitis, chronic villitis, maternal hypertension, and adverse outcomes in subsequent pregnancies are apparent. This information may be useful in patient counseling.

Chronic villitis of unknown etiology in twin gestations.

Chronic villitis of unknown etiology (CVUE) is a frequently encountered placental lesion associated with poor pregnancy outcome. We examined 22 twin placentas with CVUE to determine its distribution and clinicopathological significance in twin gestations. CVUE affected both twins' placental portions with an approximately equal degree of severity in 12 of 22 cases (9 dichorionic, 3 monochorionic). Only one twin's placental portion was affected in 8 cases (8 dichorionic). In the remaining 2 (1 dichorionic, 1 monochorionic), both placental portions were affected, but the CVUE was significantly more severe in one. The CVUE varied in extent from rare foci to diffuse involvement. Seven of the 22 (32%) pairs of twins had intrapair weight differences of 15% or greater, and 14 pairs were premature. The twins with placental involvement by CVUE had a lower mean birthweight than their cotwins with less or no CVUE; however, these results were not statistically significant. CVUE may affect placentas from one or both twins, and may be a cause of discordant twin size.

Placental lesions in maternal autoimmune diseases.

We have investigated the presence and clinical implications of maternal vascular lesions and chronic villitis of unknown etiology (CVUE) in 18 placentas of 15 mothers with several autoimmune diseases (AD), including, for the first time, idiopathic thrombocytopenic purpura, autoimmune thyroid diseases, and multiple sclerosis. The group with AD had significantly more maternal vascular lesions and CVUE than the control group. We did not find lesions that could be attributed to any of the diseases in particular. The histopathologic picture was similar in these diseases, although there appears to be a spectrum in severity. Placental vascular damage with deposits of IgM, C3, and C1q was more prominent in systemic lupus erythematosus and in a patient with systemic sclerosis. In both of these diseases but not in the other conditions, these lesions were related to poor fetal outcome. Although the precise role of each of these autoimmune diseases in pregnancy and fetal outcome remains to be established, there appears to be at least one link between them represented by the presence of severe acute atherosis and heavy granular vascular deposits of IgM, C3, and C1q associated in some with poor fetal outcome. The role of CVUE remains speculative.

Chronic villitis of unknown etiology and maternal arterial lesions in preeclamptic pregnancies

Placental lesions from 361 singleton full-term pregnancies were studied. These placentas were divided into two major groups: the study group consisting of 146 placentas from mothers with pregnancy-induced hypertension and a normotensive control group, which included 215 placentas from mothers with normal pregnancies. Each group was divided into three subgroups according to the allocation of infant's birthweight in the normal ponderal curve. A statistically significant higher incidence and severity of villous lesions was observed in placentas of mothers with pregnancy-induced hypertension when infants were over the 25th centile of the ponderal curve. Vascular lesions, i.e., absence of physiological changes in spiral arteries of the placental bed, acute atherosis and chronic vasculitis-like lesions were also more frequently observed in the hypertensive group than in controls. These placental lesions have been described in placentas of small for gestational age infants with or without maternal hypertension and in those of preeclamptic women with appropriate for gestational age infants. Since acute atherosis-like lesions have been reported in placentas of pregnant women with systemic lupus erythematosus and in rejected renal transplants, a possible maternal immunological reaction against fetal tissues could be responsible for the pathogenesis of these entities.