title: Pharmacological inhibition of inflammatory pathways for the prevention of preterm birth.
abstract: The major cause of spontaneous preterm birth (sPTB) at less than 32 weeks of gestation is intrauterine inflammation as a consequence of colonisation of the gestational membranes by pathogenic microorganisms which trigger activation of the local innate immune system. This results in release of inflammatory mediators, leukocytosis (chorioamnionitis), apoptosis, membrane rupture, cervical ripening and onset of uterine contractions. Recent PCR evidence suggests that in the majority of cases of inflammation-driven preterm birth, microorganisms are present in the amniotic fluid, but these are not always cultured by standard techniques. The nature of the organism and its cell wall constituents, residence time in utero, microbial load, route of infection and extent of tissue penetration are all factors which can modulate the timing and magnitude of the inflammatory response and likelihood of progression to sPTB. Administration of anti-inflammatory drugs could be a viable therapeutic option to prevent sPTB and improve fetal outcomes in women at risk of intrauterine inflammation. Preventing fetal inflammation via administration of placenta-permeable drugs could also have significant perinatal benefits in addition to those related to extension of gestational age, as a fetal inflammatory response is associated with a range of significant morbidities. A number of potential drugs are available, effective against different aspects of the inflammatory process, although the pathways actually activated in spontaneous preterm labour have yet to be confirmed. Several pharmacological candidates are discussed, together with clinical and toxicological considerations associated with administration of anti-inflammatory agents in pregnancy.
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, King Edward Memorial Hospital, 374 Bagot Rd, Subiaco, Perth, WA 6008, Australia. jeff.keelan@uwa.edu.au
authors.forename: J A
authors.initials: JA
authors.lastname: Keelan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D002821:Chorioamnionitis; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D018743:Perinatal Care; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology / Q000517:prevention & control*; D014599:Uterus / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology
chemical_list: D000893:Anti-Inflammatory Agents