Chronic Villitis Research Articles

Immunohistochemical Study of M1 and M2 Macrophages Population in Chronic Villitis of the Placenta

Abstract Introduction Villitis is characterized by the presence of inflammatory infiltrate (CD8 lymphocyte) in the placental villous and is classified as to the etiology in known and unknown. In most cases, villitis is idiopathic (villitis of unknown etiology [VUE]) because no microorganisms are evident and there are no maternal symptoms or signs. It has recently been proposed that pregnancy is, in fact, an active and highly regulated immune process in which macrophages play an important role. Macrophages may present with M1 phenotype, important effector cells, or M2 phenotype, capable of suppressing the function of M1 macrophages and influencing immunoregulation and tissue repair. CD68 antibody recognizes macrophages M1 and M2, whereas CD11c and CD163 antibodies are specific for the identification only of M1 and M2 macrophages, respectively. The objective of our study is to characterize in human placentas in the subpopulation of M1 and M2 macrophages in VUE. Methods Sixteen cases of chronic villitis (all without an identifiable etiologic agent) and three control placentas were examined using immunohistochemistry with antibodies for CD68, CD11c, CD163, and CD3. Results CD68 and CD163 were present in all cases in the normal areas. CD68, CD163, and CD11c were present in the villous stroma and in the intervillous space in the inflamed areas. The percentage of CD68-positive macrophages was higher than CD163- and CD11c-positive macrophages in all specimens studied. A total increase of CD68, CD163, and CD11c with the predominance of CD11c over CD163 in the inflamed areas was observed. Conclusion The predominance of M1 macrophages (CD11c) in the inflamed areas suggests the influence of these cells in the pathogenesis VUE. The higher amount of M2 (CD163) in the inflamed villous compared to normal areas suggests a possible immunoregulatory mechanism of the inflammatory process in VUE.

Trophoblast communication with distant cells – messaging via extracellular vesicles and non-coding RNA

Cytomegalovirus (CMV) infection is the most common cause of congenital viral infections in humans. The unusual structure of the placenta plays a pivotal role in CMV transmission from mothers to fetuses. The aim of this study was to evaluate the histopathological findings of placentas with congenital CMV infections.We obtained placental specimens from 35 women who had newborns with congenital CMV infections. Placental specimens, extraplacental membranes, and umbilical cords were stained with hematoxylin and eosin, and subjected to immunohistochemical analysis. We evaluated the localization of CMV-infected cells and other histological parameters.Thirty (86%) of the 35 placentas tested positive for CMV-infected cell proteins by immunohistochemistry. A majority of CMV-positive cells were present in fibroblasts and endothelial cells in the villi. The number of CMV-infected cells was inversely correlated to gestational age at delivery. The frequency of chronic villitis (65% vs. 11%; p < 0.01) and changes of the villi (38% vs. 0%; p < 0.05) in the placentas from mothers with symptomatic congenital CMV infections was higher than those observed in samples from mothers with asymptomatic congenital infections. The frequency of changes of the decidua (43% vs. 5%; p < 0.01) in the placentas from mothers with non-primary CMV infections was higher than those from mothers with primary infections.Chronic villitis and changes of the villi were associated with symptomatic congenital CMV infections. The changes of the decidua were associated with congenital CMV infections, in mothers with non-primary CMV infections.

Utility of First Trimester Maternal Serum Alpha Fetoprotein to Predict Placental Ischemic Disease [18S

INTRODUCTION: While elevated second trimester maternal serum alpha fetoprotein (msAFP) has been associated with adverse pregnancy outcomes, the utility of first trimester msAFP for prediction of placental ischemic disease is not known. We sought to investigate whether first trimester msAFP correlates with pathology findings suggestive of ischemic placental disease. METHODS: An IRB-approved, multi-site retrospective cohort study was performed among patients with first trimester msAFP as part of routine aneuploidy screening and subsequent placental evaluation from April 2015-August 2016. Pathology report findings were reviewed and classified according to placental diagnostic criteria by the Perinatal Section of the Society for Pediatric Pathology. This classification included 1) amniotic fluid infection 2) maternal underperfusion 3) fetal vascular thrombo-occlusive disease and 4) inflammatory changes (ie. chronic villitis). Spearman correlation coefficient determined the relationship between first trimester msAFP and placental weight. Chi-square and Fisher exact test determined whether an elevated first trimester msAFP is associated with placental pathologic findings. RESULTS: We evaluated 368 patients with first trimester msAFP and placental pathology reports available for review. First trimester msAFP >2.0 MoM is predictive of a placental weight <10th percentile and is suggestive of placental ischemic disease 81.6% vs 57.7% (OR 3.24, 95% CI 1.37-7.66). First trimester msAFP > 2.0 is also associated with pathology findings consistent with fetal vascular occlusive disease 21.4% vs 6.1% (OR 4.17, 95% CI 1.76-9.91). CONCLUSION: Elevated first trimester msAFP is predictive of placental insufficiency and placental ischemic disease which can help identify at risk pregnancies in the first trimester.

Basal Chronic Villitis and Disorders of the Placental Basal Plate: A Possible Immunological Link Between Hypertensive Disorders of Pregnancy and Morbidly Adherent Placenta.

Hypertensive disorders of pregnancy (HDP) are a common cause for preterm delivery. Prior studies showed that chronic villitis (CV) is associated with intrauterine growth restriction, preeclampsia, intrauterine fetal death, and morbidly adherent placenta (MAP). The authors hypothesize that disorders of the placental basal plate, especially basal chronic villitis (BCV), are associated with HDP. The laboratory information system was queried over 12 years to identify placentas with or without the clinical history of HDP and with or without multifocal/focal CV or BCV. As a control for tissue sampling, a similar search was performed over 5 years for placentas evaluated for MAP. Of 19,683 placentas identified, 14.8% had CV which was in 18.5% and 14.2% of placentas associated with or without HDP, respectively, a significant difference (P < .0001). BCV was present in 6.0% and 3.9% of placentas with or without HDP, respectively, also a significant difference (P < .0001). BCV was more likely than multifocal/focal CV to occur in HDP (32.4% vs 27.4%) when all cases of CV were analyzed (P = .025). Of 221 placentas with MAP, 64% had multifocal/focal CV and 36% had BCV. BCV and CV are more common in placentas with HDP than in normotensive pregnancies. They are also seen in MAP, as supported by another recent study.

Histopathological analysis of placentas with congenital cytomegalovirus infection

IntroductionCytomegalovirus (CMV) infection is the most common cause of congenital viral infections in humans. The unusual structure of the placenta plays a pivotal role in CMV transmission from mothers to fetuses. The aim of this study was to evaluate the histopathological findings of placentas with congenital CMV infections. MethodsWe obtained placental specimens from 35 women who had newborns with congenital CMV infections. Placental specimens, extraplacental membranes, and umbilical cords were stained with hematoxylin and eosin, and subjected to immunohistochemical analysis. We evaluated the localization of CMV-infected cells and other histological parameters. ResultsThirty (86%) of the 35 placentas tested positive for CMV-infected cell proteins by immunohistochemistry. A majority of CMV-positive cells were present in fibroblasts and endothelial cells in the villi. The number of CMV-infected cells was inversely correlated to gestational age at delivery. The frequency of chronic villitis (65% vs. 11%; p < 0.01) and changes of the villi (38% vs. 0%; p < 0.05) in the placentas from mothers with symptomatic congenital CMV infections was higher than those observed in samples from mothers with asymptomatic congenital infections. The frequency of changes of the decidua (43% vs. 5%; p < 0.01) in the placentas from mothers with non-primary CMV infections was higher than those from mothers with primary infections. DiscussionChronic villitis and changes of the villi were associated with symptomatic congenital CMV infections. The changes of the decidua were associated with congenital CMV infections, in mothers with non-primary CMV infections.

Placental Cytomegalovirus Infection.

In the United States, cytomegalovirus is the most common congenital viral infection and the number 1 cause of nonhereditary sensorineural hearing loss. The vast majority of infants may be asymptomatic, especially if cytomegalovirus is contracted later in the pregnancy, and some symptoms may have a delayed onset. Therefore, it is important for the pathologist to identify the common histologic findings to help confirm the diagnosis so the child can be followed for late sequelae. Histologic examination of the placenta is important in live births and in cases of intrauterine fetal demise. Chronic lymphoplasmacytic villitis and fibrotic, avascular villi are the most common findings. When present, Cowdry A intranuclear and basophilic intracytoplasmic inclusions are characteristic. Immunohistochemistry for cytomegalovirus can highlight these inclusions as well as the associated eosinophilic debris. In addition, polymerase chain reaction or viral culture on placental or fetal samples can be performed for confirmation.

Defining early vs late fetal growth restriction by placental pathology.

Although early and late fetal growth restriction have been suggested to be distinct entities, the optimal gestational age cut-off that differentiates the two conditions is currently unclear and has been arbitrarily set in previous studies between 32 and 37weeks. We aimed to use placental pathology findings to determine that optimal gestational age cut-off between early and late fetal growth restriction. A retrospective cohort study of all women with singleton gestation who gave birth to a neonate diagnosed as small-for-gestational age (small-for-gestational age, defined as birthweight <10th percentile for gestational age) at a tertiary referral center between January 2001 and December 2015, and for whom placental pathology was available. Placental abnormalities were classified into lesions associated with maternal vascular malperfusion (MVM), fetal vascular malperfusion, placental hemorrhage and chronic villitis. Placental findings were analyzed as a function of gestational age at birth. The analysis was repeated in the subgroups of women without hypertensive complications of pregnancy (to reflect changes associated with isolated small-for-gestational age) and of neonates with severe small-for-gestational age (defined as birthweight <5th percentile), which are more likely to represent true fetal growth restriction. A total of 895 women met the inclusion criteria. The only histological finding that changed with gestational age was MVM pathology, which decreased in frequency with increasing gestational age. We identified a considerable drop in the rate of MVM lesions at 33weeks of gestation. The rate of MVM pathology in placentas of infants born before 330/7 weeks was significantly higher than that observed in placentas of infants born at 330/7 weeks or longer: 71.6% vs 27.4%, P<0.001 for ≥2 MVM lesions, and 35.5% vs 3.5%, P<0.001 for ≥3 MVM lesions. These findings persisted in the subgroups of women without hypertensive complications of pregnancy (n=662) and of neonates with severe small-for-gestational age (n=464). Using placental pathology as a direct measure of the mechanisms underlying fetal growth restriction, the optimal gestational age at birth cut-off which differentiates early from late fetal growth restriction appears to be 330/7 weeks.

Placental inflammation, lifestyle, maternal and early child sensitisation to allergens - the assessment of lifestyle and allergic disease during infancy birth cohort.

To investigate (i) whether maternal sensitisation to allergens, and lifestyle can influence the risk of acute and chronic inflammation of the placenta, in the forms of chorioamnionitis and villitis, respectively, and (ii) whether these placental inflammations are associated with the outcome of sensitisation for the child during preschool age. Placentas from term uncomplicated pregnancies (n=275) in the assessment of lifestyle and allergic disease during infancy study were analysed for the presence of acute chorioamnionitis and chronic villitis. Stepwise logistic regression was performed to estimate the relative risk of placental inflammation in relation to maternal allergic sensitisation and lifestyle, and the association between placental inflammation and sensitisation of the child up to five years of age. Parity and delivery at home were independently associated with chorioamnionitis, home delivery only with the low grade. Maternal allergic sensitisation was associated with increased risk of villitis in the bivariable model, however, not in the multivariable model. No significant associations were detected between placental inflammation and the outcome of sensitisation to allergens at five years of age. Our data do not support the hypothesis that the increased risk for sensitisation of a child when the mother is allergic is mediated via placental inflammation.

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.

The differences in placental pathology and neonatal outcome in singleton vs. twin gestation complicated by small for gestational age.

We aimed to compare placental histopathology and neonatal outcome between dichorionic diamniotic (DCDA) twins and singleton pregnancies complicated by small for gestational age (SGA). Medical files and placental pathology reports from all deliveries between 2008 and 2017 of SGA neonates, (birthweight < 10th percentile), were reviewed. Comparison was made between singleton pregnancies complicated with SGA (singletons SGA group) and DCDA twin pregnancies (Twins SGA group), in which only one of the neonates was SGA. Placental diameters were compared between the groups. Placental lesions were classified into maternal and fetal vascular malperfusion lesions (MVM and FVM), maternal (MIR) and fetal (FIR) inflammatory responses, and chronic villitis. Neonatal outcome parameters included composite of early neonatal complications. The twins SGA group (n = 66) was characterized by a higher maternal age (p = 0.011), lower gestational age at delivery (34.9 ± 3.1 vs. 37.7 ± 2.6weeks, p < 0.001), and a higher rate of preeclampsia (p = 0.010), compared to the singletons SGA group (n = 500). Adverse composite neonatal outcome was more common in the twins SGA group (p < 0.001). Placental villous lesions related to MVM (p < 0.001) and composite MVM lesions (p = 0.04) were more common in the singletons SGA group. On multivariate logistic regression analysis, the singletons SGA group was independently associated with placental villous lesions (aOR 3.6, 95% CI 1.9-7.0, p < 0.001) and placental MVM lesions (aOR 2.44, 95% CI 1.29-4.61, p = 0.006). Placentas from SGA singleton pregnancies have more MVM lesions as compared to placentas from SGA twin pregnancies, suggesting different mechanisms involved in abnormal fetal growth in singleton and twin gestations.

Recurrent Pregnancy WastageHistology of Products of Conception

Background: Histopathologic examination of products of spontaneous abortion is done to identify pregnancy- molar or ectopic. Also, in the perspective of recurrent abortion, additional diagnostic information can be obtained. We studied products of conception with the aim to find if it is of any value in recurrent pregnancy wastage. Methods: Data was obtained from patients with the diagnosis of recurrent spontaneous abortion. The samples were examined macroscopically and microscopically by a competent histopathologist. Results: Age of the patients ranged from 23-36 years. Majority of the recurrent abortions occurred during 10-15 weeks of gestation accounting for 41 (65.07%) cases. Recurrences ranged from third to fifth time loss contributing to 44 (69.84%), 14 (22.22%) and 5 (7.93%) cases respectively. Villous oedema of chorionic villi were seen in 30 (47.61%) cases. Abnormal vascularity in the form of complete avascularity of villi was observed in 8 (12.69%) cases. 50 (79.36%) cases showed fibrinoid degeneration. Amongst the 50 cases, 30 (60%) cases showed both perivillous and intravillous fibrin while 20 (40%) cases showed only perivillous fibrin deposition. 30 cases (47.61%) showed evidence of chronic villitis. The 30 cases were subdivided into “infectious villitis“ and “villitis of unknown etiology“ (VUE). Infectious villitis was seen in only 1 case (3.3%) which showed presence of toxoplasmal cysts and plasma cell infiltration. Deciduitis was observed in 31 (49.20%) cases. Decidual necrosis was seen in 23 (36.50%) cases. 3 (4.76%) cases of partial mole were diagnosed. 4 (6.34%) cases each of syncitial knots and villous infarction were seen. We did not encounter any cases of chronic intervillositis and chronic endometritis. Conclusion: It is rational to perform histopathological examination routinely for all recurrent miscarriages.

The role of placental malperfusion in the pathogenesis of preeclampsia in dichorionic twin and singleton pregnancies

IntroductionIn singletons, the pathogenesis of hypertensive disorders of pregnancy (HDP) is attributed to abnormal placentation, characterized by maternal vascular malperfusion (MVM) lesions. Whether MVM plays a similar role in twin pregnancies is unclear. The purpose of the study was to compared placental pathology findings between dichorionic-twin and singleton pregnancies complicated by HDP. MethodsRetrospective cohort study of women with dichorionic-twin or singleton pregnancies complicated by HDP who gave birth in a single tertiary center between 2001 and 2015. Placental abnormalities were classified into lesions associated with MVM, fetal vascular malperfusion, placental hemorrhage and chronic villitis. Placental findings and neonatal outcomes were compared between twin and singleton pregnancies. ResultsA total of 144 women with twins and 768 women with a singleton pregnancy met the inclusion criteria. Compared with HDP singletons, twins with HDP had higher mean birth weights, were less likely to be small for gestational age and be born at <34 and at <32 weeks. Twins had lower odds for placental weight below <10th percentile (aOR 0.49, 95%CI 0.33–0.71), for MVM pathology (aOR 0.28, 95%CI 0.20–0.39) and for fetal vascular malperfusion pathology (aOR 0.65, 95%CI 0.45–0.93). These finding remained significant in the subpopulation of early onset HDP (<34 weeks) and small for gestational newborn. DiscussionOur findings support the hypothesis that MVM are less relevant to the pathogenesis of HDP in twin pregnancies and suggest that other placental or non-placental factors are responsible for the increased risk of HDP in twin pregnancies.

Association of Maternal Prepregnancy Body Mass Index With Placental Histopathological Characteristics in Uncomplicated Term Pregnancies.

IntroductionPrepregnancy obesity is a growing global health problem and has several risks for mother and child. The aim of this study was to systematically examine the effect of increased maternal body mass index (BMI) on placental pathology in otherwise uneventful term pregnancies.MethodsIn this analysis, we studied data of the Netherlands Amniotic Fluid study, a prospective study of women delivering in Utrecht, the Netherlands, between 2006 and 2007. We included women with uncomplicated pregnancies, vaginal delivery, and data on prepregnancy weight and height (n = 382). Placental histopathology was compared between women of normal BMI (≤24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2).ResultsIncreasing prepregnancy BMI was associated with heavier placentas and higher mean infant’s birth weight. In addition, obesity was positively associated with high-grade chronic villitis (odds ratio [OR]: 18.1, 95% confidence interval [CI]: 1.6–205.2), accelerated villous maturation (OR: 1.1, 95% CI: 1.0–1.2), and lower incidence of placental weight below the 10th percentile for gestational age (OR: 0.5, 95% CI: 0.3–1.0). There was a substantial effect of parity on maternal, placental, and neonatal weights.ConclusionsEven in uncomplicated pregnancies, maternal obesity is associated with characteristic changes in placental pathology. Further research is needed to evaluate these changes in view of later-life health of infants born to obese mothers.

Histological Analysis of Term Placentas from Hyperimmune Globulin-Treated and Untreated Mothers with Primary Cytomegalovirus Infection

Background: The Congenital Human Cytomegalovirus Infection Prevention (CHIP) study, a randomized, blinded, placebo-controlled trial, demonstrated that the efficacy of hyperimmune globulin (HIG) was not different from that of placebo regarding transmission of cytomegalovirus (CMV) from mothers to newborns. Our aim was to analyze histologically HIG effects on placentas collected for the CHIP study. Materials and Methods: Virological and histological analyses were performed on 40 placentas from transmitter and nontransmitter HIG-treated and untreated mothers by assessing the number of CMV-positive cells, tissue viral load, tissue damage, and compensatory mechanisms. Results: The HIG and placebo groups showed no significant differences in the number of CMV-positive cells (median number in 10 fields at 10 high-power fields: 2.5 vs. 2, p = 0.969) and viral load (median load: 5 copies/5 ng vs. 10.5 copies/5 ng, p = 0.874). Regarding histological examination, the scores of parameters related to tissue damage and hypoxic parenchymal compensation were higher in transmitters except for chorangiosis, with statistically significant differences observed for chronic villitis (p = 0.007), calcification (p = 0.011), and the total score of tissue damage (p < 0.001). The HIG and placebo groups showed no significant differences for all tissue damage and compensation parameters and overall scores. Discussion: HIGs are not able to reduce placental viral load and histological damage, which was significantly associated only with infection.

Oxidative stress in placental pathology

The most important function of the placenta is the exchange of nutrients and oxygen between a mother and her fetus. To establish a healthy functioning placenta, placentation needs to occur with adequate remodelling of spiral arteries by extravillous trophoblasts. When this process is impaired, the resulting suboptimal and inadequate placenta function results in the manifestation of pregnancy complications. Impaired placenta function can cause preeclampsia and leads to fetal growth restriction due to hypoxia. Presence of hypoxia leads to oxidative stress due to an imbalance between reactive oxygen species and antioxidants, thereby causing damage to proteins, lipids and DNA. In the placenta, signs of morphological adaptation in response to hypoxia can be found. Different placental lesions like maternal or fetal vascular malperfusion or chronic villitis lead to a decreased exchange of oxygen between the mother and the fetus. Clinically, several biomarkers indicative for oxidative stress, e.g. malondialdehyde and reduced levels of free thiols are found. This review aims to give an overview of the causes and (potential) role of placental oxidative stress in the development of placental parenchymal pathology and its clinical consequences. Also, therapeutic options aiming at prevention or treatment of hypoxia of the placenta and fetus are described.

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

Placental Findings in Singleton Stillbirths: A Case-control Study.

This prospective observational study compared placental lesions of stillbirth cases and live birth controls, and aimed to determine the cause of stillbirth. The study enrolled 85 stillbirths and 85 live births at the time of delivery. There was significantly increased incidence of placental abruption (p = 0.005) and gestational diabetes (p = 0.032) in mothers with stillbirths. Histopathological examination of placenta was significantly abnormal in stillbirths compared with live births (p = 0.004). Delayed villous maturation was significantly more in stillbirths (38.82 vs. 16.47%; p = 0.002). Acute (30.59 vs. 16.47%; p = 0.04) and chronic diffuse villitis (16.47 vs. 4.7%; p = 0.02), chorionic plate acute vasculitis (28.235 vs. 14.11%; p = 0.04) were significantly more in stillbirths. Foetal vascular thrombi in the chorionic plate (30.58 vs. 14.12%; p = 0.02) and avascular villi (24.7 vs. 8.23%; p = 0.006) were significantly more in stillbirths. These abnormal placental patterns could provide information about the etiopathogenisis in stillbirths of unknown aetiology.

The placental component and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus

ObjectiveWe aimed to compare placental histopathological lesions and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus (GDM). MethodsMaternal characteristics, neonatal outcomes, and placental histopathology reports of pregnancies complicated by GDM, between 1/2008-10/2016, were reviewed. Results were compared between singletons (singleton group) and dichorionic-diamniotic twins (twin group). Placental lesions were classified as placental weight abnormalities, maternal and fetal vascular malperfusion lesions (MVM, FVM), inflammatory lesions, and lesions associated with chronic villitis. LGA was defined as birth-weight ≥90th percentile. Composite adverse neonatal outcome was defined as one or more early neonatal complications. ResultsCompared with the twin group (n = 57), the singleton group (n = 228) was characterized by higher gestational-age (38.6 ± 0.9 vs. 35.1 ± 1.8 weeks, p < 0.001) and a higher rate of insulin treatment (32.9% vs. 17.5%, p = 0.023). Placentas from the singleton group were characterized by higher rates of MVM lesions (54.4% vs. 30.7%, p < 0.001), villitis of unknown etiology (VUE, 5.7% vs. 0.9%, p = 0.040), villous immaturity (10.1% vs. 0.9%, p = 0.001), and placental weight <10th percentile (16.7% vs. 8.8%, respectively, p = 0.049). Using multivariable regression analysis, MVM (aOR = 2.2, 95% CI = 1.6–4.1), VUE (aOR = 1.2, 95% CI = 1.1–2.1), villous immaturity (aOR = 2.3, 95% CI 1.8–7.6), and placental weight <10th percentile (aOR = 1.1, 95% CI = 1.02–1.6), were the only lesions associated with singleton pregnancies. Composite adverse neonatal outcome was more common in the twin group (54.3% vs. 14.0%, p < 0.001) and it was associated only with lower GA (aOR = 3.7, 95% CI 2.1–7.3). ConclusionHigher rate of placental weight <10th percentile, MVM lesions, villous immaturity, and VUE characterize GDM singleton pregnancy as compared to twins GDM gestation, suggesting different placental alterations in the diabetic environment.

Placental pathology and neonatal outcome in small for gestational age pregnancies with and without abnormal umbilical artery Doppler flow

ObjectiveTo compare neonatal outcome and placental pathology in cases of small for gestational age (SGA) according to umbilical artery (UA) Doppler flow. Study designPregnancy and placental reports of SGA neonates (birth-weight <10th), born between 2008 and 2017 were compared between cases with normal and abnormal UA Doppler indices. Placental lesions were classified to malperfusion lesions and inflammatory responses. ResultsThe abnormal Doppler group (n = 66) delivered at an earlier gestational age, compared to the normal Doppler group (n = 92). Placentas from the abnormal Doppler group were characterized by a higher rate of maternal malperfusion lesions, while placentas from the normal Doppler group exhibited a higher rate of chronic villitis. Neonatal outcome was independently associated with abnormal Doppler, gestational age and birth weight <5th percentile. ConclusionSGA may involve a vascular mechanism, associated with abnormal Doppler flow and placental malperfusion, and an inflammatory mechanism, with normal Doppler flow and chronic villitis.

D2-40/podoplanin expression in chronic villitis of the placenta

ABSTRACT D2-40/podoplanin (D2-40/PDPN) is a multifunctional protein that can be expressed in lymphatic endothelium and immune cells. D2-40/ PDPN expression in chronic villitis (CV) has not been studied. In 22 cases of CV, we analyzed both D2-40/PDPN expression as well as its coexpression with immune cells markers, and the relationship with stromal cells. In the non-inflamed villi, the D2-40/PDPN positive plexiform pattern has a lymphatic-like conductive network. In the inflamed villi, the D2-40/PDPN expression, predominantly restricted to stromal cells forming a cellular network, is likely related to a phase of the inflammatory response, such as reorganization of the damaged tissue.