Dual roles of amniotic fluid nitric oxide and prostaglandin E₂ in preterm labor with intra-amniotic infection

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 intra-amniotic infection (NOx: median 1.8 μmol/mg creatinine, range 0.7 to 6.8 vs. 1.3 μmol/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.