title: 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. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that "sterile" intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by "danger signals," is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are 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 present in 3-5% of term placentas and in 94% of placentas delivered at 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 of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, 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 disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI.
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI. Electronic address: romeror@mail.nih.gov.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Noppadol
authors.initials: N
authors.lastname: Chaiyasit
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI; Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Yeon Mee
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D001424:Bacterial Infections / Q000150:complications*; D002177:Candidiasis / Q000150:complications; D018925:Chemokines / Q000378:metabolism*; D002821:Chorioamnionitis / Q000453:epidemiology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology; D015995:Prevalence; D047929:Term Birth; D009626:Terminology as Topic
chemical_list: D018925:Chemokines
keywords: CXCL6; chorionic vasculitis; fetal inflammatory response syndrome; granulocyte chemotactic protein; interleukin (IL)-8; microbial invasion of the amniotic cavity; placental pathology; pregnancy; prematurity; preterm; staging; sterile inflammation