Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance

Abstract

Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis, and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intra-amniotic infection has been generally considered to be the cause of acute histologic chorioamnionitis and funisitis; however, recent evidence indicates that “sterile” intra-amniotic inflammation, which occurs in the absence of demonstrable microorganisms but can be induced by “danger signals”, is frequently associated with these lesions. In the context of intra-amniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient favoring the migration of neutrophils from maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and is present in 3-5% of placentas delivered at term, but in 94% of placentas delivered between 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks for the fetal inflammatory response syndrome, a condition characterized by an elevation in fetal plasma concentrations of interleukin-6, associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multi-organ fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.

Procalcitonin is more likely to be released by the fetus rather than placental tissue during chorioamnionitis

“…Rapid diagnosis and management of HCA are essential [9][10][11] . Unfortunately, clinical signs of HCA and microbiological assessment of the amniotic fluid appear to be unreliable diagnostic critera 2,3 .…”

Myometrial cytokines and their role in the onset of labour

“…CA is a robust inflammatory response to intraamniotic infection, and commonly associated with an infiltration of neutrophils in response to IL-8 and CXCL-6, amongst other chemokines (Kim et al 2015b). Damageassociated molecular pattern molecules (see below) are also able to induce such neutrophil-attracting chemokine, which led to the possibility of a mutual parturition pathway.…”

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

“…Microbial invasion and neutrophil migration can progress to cord inflammation (funisitis) and fetal invasion. These events produce a fetal inflammatory response syndrome (FIRS), with potential damage to the fetal brain, lung, gastrointestinal tract and skin [16][17][18] that can lead to long-term complications after birth and beyond childhood [17]. Funisitis causes a significant increase in pro-inflammatory cytokines (IL-1β, IL-6 and IL-8) in cord blood of premature infants [19].…”

“…Intrauterine inflammation most commonly results from chorioamnionitis, which is defined as inflammation of the fetal membranes (chorion and amnion) and placenta [16]. Microbial invasion of the amniotic cavity and danger signals of non-microbial origin induce a robust local inflammatory response, with high levels of pro-inflammatory cytokines that promote neutrophil recruitment [16].…”

“…For many infants, exposure to inflammation begins during fetal life, especially for those born prematurely [16]. Intrauterine inflammation most commonly results from chorioamnionitis, which is defined as inflammation of the fetal membranes (chorion and amnion) and placenta [16].…”