title: Dual roles of amniotic fluid nitric oxide and prostaglandin E2 in preterm labor with intra-amniotic infection.
abstract: We hypothesized that induction of nitric oxide synthase and cyclo-oxygenase-2 by bacterial products in intra-amniotic infection could increase the production of proinflammatory nitric oxide and prostaglandin E2 (PGE2) and cause preterm labor. Thus, we sought to determine amniotic fluid levels of nitric oxide metabolites (NOx) and PGE2 in preterm labor patients with and without intra-amniotic infection. Amniotic fluid from 13 preterm labor patients with intra-amniotic infection and 24 without intra-amniotic infection were studied. Intra-amniotic infection was defined as the presence of a positive amniotic fluid culture. Amniotic fluid was tested for NOx, PGE2, glucose, leukocyte counts, Gram stains, creatinine, pH, and specific gravity. NOx was determined using Griess reagent after reduction of nitrate to nitrite with aspergillus nitrate reductase. PGE2 was measured by an enzyme-linked immunoassay. Both amniotic fluid NOx and PGE2 were normalized by amniotic fluid creatinine. We found that amniotic fluid concentrations of NOx and PGE2 were significantly higher in preterm labor patients with intra-amniotic infection compared to those without intraamniotic infection (NOx: median 1.8 micromol/mg creatinine, range 0.7 to 6.8 vs. 1.3 micromol/mg creatinine, range 0.9 to 2.1, p=0.03; PGE2: median 33.5 ng/mg creatinine, range 0.0 to 1048.6 vs. 0.0 ng/mg creatinine, range 0.0 to 33.6, p=0.004). In addition, amniotic fluid NOx and PGE2 were positively correlated (r=0.343, p=0.0398). We conclude that there may be an interaction between the nitric oxide and prostaglandin pathways in intraamniotic infection. Increased production of amniotic fluid pro-inflammatory nitric oxide and PGE2 may play an important role in the pathogenesis of preterm labor in patients with intra-amniotic infection.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Hsu
authors.forename: E
authors.initials: E
authors.lastname: Meaddough
authors.forename: K
authors.initials: K
authors.lastname: Aversa
authors.forename: S F
authors.initials: SF
authors.lastname: Hong
authors.forename: I S
authors.initials: IS
authors.lastname: Lee
authors.forename: R O
authors.initials: RO
authors.lastname: Bahodo-Singh
authors.forename: L C
authors.initials: LC
authors.lastname: Lu
authors.forename: J A
authors.initials: JA
authors.lastname: Copel
mesh_terms: D000293:Adolescent; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002821:Chorioamnionitis / Q000175:diagnosis / Q000378:metabolism*; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000378:metabolism*; D011247:Pregnancy; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D015232:Dinoprostone