Adverse perinatal outcomes of chronic intervillositis of unknown etiology: an observational retrospective study of 122 cases

Abstract

our study aimed to assess perinatal outcomes and recurrence rate of chronic intervillositis of Unknown etiology (ciUe). We conducted an observational retrospective study in a tertiary care university hospital in France from January 1, 1997 to July 31, 2018. 122 pregnancies (102 women) with CIUE were included. Cases of the Department of Histopathology placenta database were re-analysed independently by three pathologists specializing in fetal pathology. Diagnosis of CIUE was confirmed according to: (1) the presence of cellular infiltrate in the intervillous space, (2) ~ 80% of the mononuclear cells in the intervillous space positive for CD68, (3) infiltration occupying at least 5% of the intervillous space, and (4) no clinical or histopathological sign of infection. Outcomes of pregnancies with CIUE (miscarriages, stillbirths, terminations of pregnancy, live birth with or without prematurity or fetal growth restriction) and proportion of ciUe recurrence were analysed. the lost pregnancies comprised 17 (13.9%) miscarriages, 17 (13.9%) stillbirths, and 18 (14.8%) terminations of pregnancy. Of the 70 (57.4%) pregnancies that led to a live birth, 38 (54.3%) new-borns were premature and 50 (72.5%) exhibited fetal growth restriction. Among the 102 women, 23 subsequently became pregnant, half of whom (n = 11) developed recurrent CIUE. CIUE was associated with high rates of adverse perinatal outcomes, including pregnancy loss, fetal growth restriction, and preterm birth with a risk of recurrence nearly 50%. Abbreviations aPL Antiphospholipid AZA Azathioprine BMI Body mass index CIUE Chronic intervillositis of unknown etiology HCQ Hydroxychloroquine HES Hematoxylin-eosin-saffron FGR Fetal growth restriction LDA Low-dose aspirin LMWH Low-molecular-weight heparin TOP Termination of pregnancy MVM Maternal vascular malperfusion of the placental bed PIg Polyvalent immunoglobulin

Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants

“…51 Referred to by a variety of differing terms in the medical literature, chronic histiocytic intervillositis has remained a condition of unknown etiology that has a high rate of recurrence and association with poor obstetric outcomes that include miscarriage, fetal demise, intrauterine growth restriction, and preterm delivery. 52,53 It is an unusual placental abnormality, and although its exact prevalence is unknown, prior to the COVID-19 pandemic it had been estimated to occur in approximately 6 of 10,000 (0.6%) 2 nd and 3 rd trimester placentas. 52,54 The pathology features consist of the accumulation of mononuclear inflammatory cells in the intervillous space of the placenta, which are predominantly histiocytes and stain positive by immunohistochemistry with anti-CD68 and other markers of histiocytes and macrophages.…”

“…52,53 It is an unusual placental abnormality, and although its exact prevalence is unknown, prior to the COVID-19 pandemic it had been estimated to occur in approximately 6 of 10,000 (0.6%) 2 nd and 3 rd trimester placentas. 52,54 The pathology features consist of the accumulation of mononuclear inflammatory cells in the intervillous space of the placenta, which are predominantly histiocytes and stain positive by immunohistochemistry with anti-CD68 and other markers of histiocytes and macrophages. Histiocytes typically comprise greater than 80% of the inflammatory cell population in the intervillous space, but there is often a lymphocyte population also present, and occasionally neutrophils.…”

“…Among the 5 stillborn infants in our study, all of their placentas were characterized by a marked increase in perivillous fibrin in addition to having chronic histiocytic intervillositis and syncytiotrophoblast necrosis -several had the appearance of massive perivillous fibrin deposition. Based upon studies of obstetrical outcomes from chronic histiocytic intervillositis prior to the COVID-19 pandemic, 52,53,56 it can be hypothesized that increased fibrin resulted in placental malperfusion that contributed to the deaths of some of the fetuses in this study.…”

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

“…Chronic chorioamnionitis is also associated with fetal death (117,152). Chronic intervillositis of unknown etiology is a strongly associated with miscarriage, intrauterine fetal demise and a very high risk of recurrence (141,(153)(154)(155). Women with a history of recurrent CIUE have gone on to successful live birth after treatment with aspirin and low molecular weight heparin (LMWH), aspirin and corticosteroids, aspirin, LMWH, and steroids, or aspirin, prednisone, LMWH and hydroxychloroquine (147,156,157).…”

“…Villitis of unknown etiology is associated with fetal growth restriction, low birth weight and small for gestational age (110,117,160). Chronic intervillositis of unknown etiology is the other chronic inflammatory pathology frequently associated with disorders of fetal growth (155,(161)(162)(163). Multiple studies demonstrate outcomes of fetal growth restriction with rates of 70% or higher when CIUE is present (155,161,162).…”