Recent advances in elucidating the pathogenesis of preterm delivery, the detection of patients at risk, and preventative therapies.
Preterm deliveries (PTDs) are a leading cause of neonatal morbidity and mortality in the world. Efforts to prevent PTD have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools, and generally ineffective therapies. There is increasing clinical and laboratory evidence that many PTDs result from premature activation of cells in the cervix, decidua, and fetal membranes in response to local mediators of maternal or fetal stress, ascending genital tract infection, and/or decidual hemorrhage. Putative mediators include peptide hormones (e.g. corticotropin releasing hormone (CRH)) and/or inflammatory-cytokines (e.g. interleukin-1, -6, and -8 (IL-1, -6 and -8)) which promote the production of oxytotic factors (e.g. prostanoids and endothelin) capable of eliciting uterine contractions and enhancing expression of proteases capable of initiating cervical change and/or membrane rupture. The identification of cervical, decidual, and/or chorionic extracellular matrix (ECM) proteins (e.g. collagen fragments and fetal fibronectin) and ECM-degrading proteases (e.g. collagenases and granulocyte elastase) in maternal serum and cervicovaginal secretions may provide new approaches to the detection of patients at high risk for PTD. In addition, our growing understanding of the pathogenic processes preceding PTD have led to new therapeutic approaches including antibiotic, anticytokine, and antiprotease treatments.
Lockwood
C J
CJ
Department of Obstetrics, Gynecology, and Reproductive Science, Mount Sinai School of Medicine, New York, New York.
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017364:Collagenases / Q000032:analysis; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D005353:Fibronectins / Q000032:analysis; D005831:Genital Diseases, Female / Q000150:complications; D006801:Humans; D007239:Infections / Q000150:complications; D007249:Inflammation; D019272:Leukocyte Elastase; D007752:Obstetric Labor, Premature / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010196:Pancreatic Elastase / Q000032:analysis; D011247:Pregnancy; D011480:Protease Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D013312:Stress, Physiological / Q000150:complications; D014592:Uterine Hemorrhage / Q000150:complications; D014626:Vaginal Smears
D000900:Anti-Bacterial Agents; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011480:Protease Inhibitors; D003346:Corticotropin-Releasing Hormone; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D017364:Collagenases