Chronic villitis of unknown etiology: Investigations into viral pathogenesis.

INTRODUCTION: Chronic 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. METHODS: We 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. RESULTS: We 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. DISCUSSION: These 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.

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

INTRODUCTION: Maternal 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 METHODS: In 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. RESULTS: Chronic 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. DISCUSSION: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.

Of pregnancies complicated by small for gestational age babies at term, what proportions have placental findings with implications for future pregnancies or neonatal outcomes?

Background: Small for gestational age (SGA) is a term to define any baby born with birth weight <10th centile. SGA can be associated with a number of placental pathology findings, which may influence maternal outcomes, neonatal neurodevelopment, and future pregnancies.Aims: To identify the proportion of term pregnancies complicated by SGA with placental findings that may have implications for future pregnancies or neonatal outcomes.Method: A retrospective review between 2011 and 2015 of babies and placentas born at term with SGA histopathological findings were categorized as to whether they had a high recurrence rate and where the long-term neurodevelopmental outcome may affect the neonate.Results: Six hundred and ninety-eight babies were identified as SGA. Only 335 (47.8%) placentas were sent for histopathological assessment. Of these, 60 (17.9%) had histopathological findings associated with high recurrence rates and 68 (20.2%) had findings associated with potential adverse neonatal outcomes.Conclusions: Of those placentas sent for examination between 17.9% and 20.2% had findings associated with either high recurrence rates or findings that may benefit from neonatal follow-up. Under 50% of pregnancies complicated by SGA at term had a placental examination, resulting in a significant number of potential important clinical consequences being missed.

Perinatal prognosis of pregnancies complicated by placental chronic villitis or intervillositis of unknown etiology and combined lesions: About a series of 178 cases.

INTRODUCTION: The objective of this work was to evaluate and compare perinatal outcomes of pregnancies complicated by placental chronic intervillositis (CIUE) or villitis (CVUE) of unknown etiology and combined lesions. METHODS: Retrospective study of all cases of significant CVUE and CIUE occurring during a 12-year period in a university tertiary hospital center. Multiple pregnancies, infectious and medical termination of pregnancies (TOP) without intra-uterine growth restriction (IUGR) were excluded. RESULTS: 178 placentas were affected (78 cases of CVUE, 24 cases of CIUE and 76 cases of combined lesions involving both villitis and intervillositis) including 12 cases of recurrence. A disorder of fetal growth was found in 73% of cases and we noted 9.5% of cases of abortion. The rate of IUGR appeared to be significantly higher in case of CIUE with a fetal death risk five times higher. These complications seems to be related to more diffuse inflammatory infiltrates (p < 0.05). CVUE was associated with a significant morbidity with 42% of severe IUGR and severe alterations of umbilical artery Doppler in nearly one third of cases. Caesarean section was important (54.8%). Sixty-one percent of newborns were hospitalized and 11.4% in neonatal reanimation. In case of combined lesions, fetal outcomes appeared relatively close to those of CVUE. CVUE could recur in more severe forms or as CIUE with an increased risk for the fetus. Clinicoanatomic correlations were noted. DISCUSSION: Observation of recurrence of CVUE on CIUE or combined lesions and similar phenotypic characteristics of the infiltrates suggest that they could be two different stages of a same disease. CVUE remains a disease to be considered as serious. Association of small lesions of intervillositis does not change the prognosis. The severity of histological lesions and the initial obstetrical accident could be discriminatory to identify patients at risk of serious recurrence. Harmonized classification will be required. CONCLUSIONS: This study confirms the higher morbidity of CIUE compared to CVUE but shows the necessity of monitoring pregnancies following an episode of CVUE, which are still at risk of serious and recurrent complications.