Dual Roles of Amniotic Fluid Nitric Oxide and Prostaglandin E₂in 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.

Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra-Amniotic Infection: A New Mechanism of Host Defense

“…16,17 In humans, intra-amniotic infection is associated with a local inflammatory response, 18 which is characterized by an increased amniotic fluid white blood cell (WBC) count [19][20][21][22][23] and elevated concentrations of inflammatory mediators, such as cytokines 18,24 and lipids (eg, prostaglandins). [25][26][27][28][29][30][31][32][33][34][35][36][37][38] In nonhuman primates, intra-amniotic infection also results in a local inflammatory response. [39][40][41][42][43][44][45][46][47][48] Neutrophils are the most abundant leukocytes in the amniotic fluid in cases of intra-amniotic infection.…”

Selected physicochemical properties of amniotic fluid according to week of pregnancy

“…In preterm labour patients, they determined higher NO metabolites (NOx: nitrate + nitrite), namely in women with an intraamniotic infection (n = 13) compared with those without infection (n = 24). The concentration positively correlated to the amniotic fl uid PGE2 concentration (26). Later (1999), the authors extended the fi ndings to the effect that NOx concentrations are signifi cantly higher in patients with a positive culture (n = 8) but are not caused by a mycoplasma agent (n = 7) compared with controls (61) (27).…”

“…A signifi cant negative correlation was observed between nitrite concentrations and the uterine artery resistance index, umbilical artery pulsatility index and umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio (19). Hsu et al (26) presented a rare application of nitrites determination in amniotic fl uid. In preterm labour patients, they determined higher NO metabolites (NOx: nitrate + nitrite), namely in women with an intraamniotic infection (n = 13) compared with those without infection (n = 24).…”

An elevated amniotic fluid prostaglandin F2αconcentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes

“…The main prostaglandins found in amniotic fluid are prostaglandin E 2 (PGE 2 ) and prostaglandin F 2α (PGF 2α ) [142, 178, 179]. The concentration of these eicosanoids increases prior to the onset of labor at term [136, 140, 142], during labor [133, 179] and rupture of the membranes [132], and in spontaneous preterm labor [particularly in the setting of microbial invasion of the amniotic cavity (MIAC)] [129–131, 137, 173, 180–187]. Despite the physiologic and pharmacologic importance of prostaglandins in spontaneous term and preterm labor, there is a paucity of literature examining the potential role of prostaglandin concentrations in the assessment of patients with preterm labor [129–131, 142, 173, 180–184, 187].…”