Maternal azithromycin therapy for Ureaplasma parvum intraamniotic infection improves fetal hemodynamics in a nonhuman primate model.

Background: Ureaplasma parvum infection is a prevalent cause of intrauterine infection associated with preterm birth, preterm premature rupture of membranes, fetal inflammatory response syndrome, and adverse postnatal sequelae. Elucidation of diagnostic and treatment strategies for infection-associated preterm labor may improve perinatal and long-term outcomes for these cases.

Objective: This study assessed the effect of intraamniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the effect of maternal antibiotic treatment on these outcomes.

Transplacental transfer of Azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model.

Background: Our goals were to describe azithromycin (AZI) pharmacokinetics in maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) following intra-amniotic infection (IAI) with Ureaplasma in pregnant rhesus monkeys and to explore concentration-response relationships.

Methods: Following intra-amniotic inoculation of Ureaplasma parvum, rhesus monkeys received AZI (12.5 mg/kg every 12 hours intravenously for 10 days; n = 10).

Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model.

Objective: We assessed the efficacy of a maternal multidose azithromycin (AZI) regimen, with and without antiinflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intraamniotic infection.

Study Design: Long-term catheterized rhesus monkeys (n = 16) received intraamniotic inoculation of U parvum (10(7) colony-forming U/mL, serovar 1). After contraction onset, rhesus monkeys received no treatment (n = 6); AZI (12.

Choriodecidual inflammation: a harbinger of the preterm labor syndrome.

Causal, cellular, and inflammatory links between choriodecidual infection with group B streptococcus (GBS) and preterm labor were assessed in a nonhuman primate model. Rhesus monkeys received varying doses of a clinical isolate of GBS, type III or saline, via an indwelling catheter placed between the chorion/decidua and myometrium in the lower pole of the uterus. Choriodecidual inoculation of GBS was followed by a graded response in amniotic fluid (AF) leukocytes, proinflammatory cytokines, prostaglandin E(2) and F(2alpha), and uterine activity (P < .

Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques.

The authors assess causal, cellular and inflammatory links between intraamniotic infection with Ureaplasma parvum or Mycoplasma hominis and preterm labor in a nonhuman primate model. Long-term catheterized rhesus monkeys received intraamniotic inoculations of clinical isolates of Ureaplasma parvum serovar 1, M hominis, media control or physiological saline. Genital mycoplasmas were quantified in amniotic fluid (AF) and documented in fetal tissues by culture and PCR.

Congenital and opportunistic infections: Ureaplasma species and Mycoplasma hominis.

There is strong evidence from clinical and experimental animal studies that ureaplasmas can invade the amnionic sac and induce an inflammatory response resulting in chorioamnionitis, preterm labor and neonatal lung injury. The ability of Ureaplasma spp. and Mycoplasma hominis to cause pneumonia, bacteremia, and meningitis in newborns can no longer be questioned.

Pretreatment with toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys.

Intrauterine infection, which occurs in most early preterm births, triggers an immune response culminating in preterm labor. The authors hypothesize that blockade of lipopolysaccharide (LPS)-induced immune responses by a toll-like receptor 4 antagonist (TLR4A) would prevent elevations in amniotic fluid (AF) cytokines, prostaglandins, and uterine contractility. Chronically catheterized rhesus monkeys at 128 to 147 days' gestation received intra-amniotic infusions of either (1) saline (n = 6), (2) LPS (0.

Relaxin and the human fetal membranes.

The human fetal membranes are complex tissues that perform many important functions during gestation. The extracellular matrix provides their strength to withstand the forces directed from the fetus and myometrium. Relaxin is a collagenolytic hormone that causes increased production of the matrix metalloproteinases.

Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model.

Objective: The purpose of this study was to determine whether treatment with ampicillin together with dexamethasone and indomethacin delays preterm birth that is induced by intraamniotic group B Streptococcus in a nonhuman primate model.

Study Design: After contraction onset that was induced by group B Streptococcus (10(6) colony-forming units/mL), chronically instrumented rhesus macaques received either no treatment (controls; n = 6); ampicillin (n = 4); or ampicillin + dexamethasone + indomethacin (n = 5). Outcomes included the interval from contraction onset until delivery and concentrations of amniotic fluid inflammatory mediators.

Proteomic analysis of cervical-vaginal fluid: identification of novel biomarkers for detection of intra-amniotic infection.

Intra-amniotic infection (IAI) is associated with preterm birth and perinatal mortality. To identify potential biomarkers, we performed a comprehensive survey of the cervical-vaginal fluid (CVF) proteome from a primate IAI model utilizing multidimensional protein identification technology (LC/LC-MS/MS) and MALDI-TOF-MS analyses. Analyses of CVF proteome identified 205 unique proteins and differential expression of 27 proteins in controls and IAI samples.

Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model.

Objectives: The purpose of this study was to determine the relative contributions of individual proinflammatory cytokines and chemokines to the triggering of preterm labor.

Study Design: Eighteen chronically instrumented pregnant rhesus monkeys at 135 +/- 3 days gestation (term = 167 days) received 1 of 5 intraamniotic infusions: (1) interleukin-1beta (IL-1beta) (10 microg; n = 5), (2) tumor necrosis factor-alpha (TNF-alpha) (10-100 microg; n = 5), (3) IL-6 (20 microg twice a day; n = 2), (4) IL-8 (20 microg twice a day; n = 2), and (5) saline control (n = 4). Primary study outcomes were the mean uterine hourly contraction area (mm Hg x s/h) in 24 hours during peak response to cytokine infusion (all groups) and the interval from cytokine infusion until labor onset (IL-1beta, IL-6, and IL-8 groups).

The diagnosis and reproductive outcome after surgical treatment of the complete septate uterus, duplicated cervix and vaginal septum.

Objective: This study was undertaken to evaluate the diagnostic management and the reproductive outcome after surgical repair of a rare reproductive malformation.

Study Design: Sixteen women with a complete septate uterus, double cervix, and a longitudinal vaginal septum were referred for evaluation. Presenting complaints were chiefly pregnancy loss in parous women (n=9) and dyspareunia in nulligravid women (n=7).

Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers.

Context: Intra-amniotic infection (IAI) is commonly associated with preterm birth and adverse neonatal sequelae. Early diagnosis of IAI, however, has been hindered by insensitive or nonspecific tests.

Objective: To identify unique protein signatures in rhesus monkeys with experimental IAI, a proteomics-based analysis of amniotic fluid was used to develop diagnostic biomarkers for subclinical IAI in amniotic fluid and blood of women with preterm labor.

Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys.

Objective: The purpose of this study was to determine whether treatment with the immune modulators dexamethasone or interleukin-10 prevents interleukin-1beta-induced uterine contractions in a nonhuman primate model.

Study Design: Thirteen chronically instrumented rhesus monkeys at 135 +/- 1 days of gestation (term, 167 days) received one of three interventions: (1) intra-amniotic interleukin-1beta (10 microg) infusion with maternal dexamethasone (1 mg/kg) intravenously every 6 hours for 1 day before interleukin-1beta and for 2 days thereafter (n = 4), (2) intra-amniotic interleukin-1beta infusion with maternal interleukin-10 (25 microg/kg) given intravenously and 100 microg interleukin-10 given intra-amniotically before the interleukin-1beta and continued every 8 hours for 3 days (n = 5), and (3) intra-amniotic interleukin-1beta administered alone (n = 5). Uterine activity was monitored continuously and quantified as the hourly contraction area (millimeters of mercury times seconds per hour) in all groups until delivery.

Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1 beta infusion in pregnant rhesus monkeys.

Objective: The purpose of this study was to examine the roles of intrauterine infection, inflammation, and spontaneous labor on the expression of matrix metalloproteinase-9 in fetal membranes and amniotic fluid of late pregnant rhesus monkeys.

Study Design: Pregnant rhesus monkeys with timed gestations were chronically catheterized to allow serial sampling of amniotic fluid before and during experimentally induced intrauterine inflammation. Six animals received group B streptococci into the chorionic-decidual space, and 4 animals received intra-amniotic interleukin-1 beta infusions (10 microg).