33: Intrauterine ureaplasma parvum and its treatment alter fetal hemodynamic status in a nonhuman primate model

Abstract

Exposure to intrauterine inflammation (IUI) is associated with adverse perinatal outcomes. IUI by Ureaplasma parvum is a predominant infectious cause of preterm birth and fetal inflammatory response syndrome (FIRS). The objective of this study was to assess whether proinflammatory mediators induced by the infection are associated with fetal hemodynamic and cardiovascular dysfunction. At preterm gestational age 127-132 days (term 165 days), long-term catheterized rhesus monkeys were assigned to the following groups: (1) control (C) (n=6); (2) infection group (IG), intra-amniotic inoculation with Ureaplasma parvum (107 CFU/ml) (n=17); and (3) treatment group (IG+A), Azithromycin (12.5 mg/kg, every 12 h, intravenous for 10 days after ) after intra-amniotic inoculation with Ureaplasma parvum (n=8). TNFα, IL1β, IL6, PGE2, and PGF2a were analyzed in the amniotic fluid by ELISA. Image-directed pulsed and color Doppler ultrasonography was utilized to obtain serial fetal hemodynamic measurements [cardiac output, EA ratio, Tei index, cerebro-placental ratio, p ulsatility index (PI)/peak systolic velocity (PSV) of umbilical artery (UA) & vein, ductus venosus, hepatic vein, inferior vena cava, aorta, ductus arteriosus, pulmonary artery (PA), and middle cerebral artery] and maternal uterine artery in utero. UA PI was significantly increased in IG comparing to C or IG+A (p = 0.005). Cardiac output in the left ventricle (LCO) was significantly decreased in IG comparing to C (p = 0.004). When the ratio of bilateral cardiac output (RCO/LCO) was obtained, there were significantly more rates of abnormal RCO/LCO (>1.6) cases in IG than C or IG+A (p = 0.020). PA PSV was significantly increased in IG comparing to C or IG+A. PGF2a levels were significantly higher in cases with abnormal UA PI (>1.1) than normal cases (p = 0.002). The value of IL6 in cases of abnormal RCO/LCO was significantly higher than in normal cases (p = 0.030). The correlation coefficient (Spearman, r) between UA PI and PGF2a was 0.6 (p = 0.015). Increase in UA PI, PA PSV and increase in RCO/LCO were observed in IG, which decreased with treatment. These hemodynamic alterations were associated with an increase in amniotic proinflammatory mediators. Ultrasound Doppler measurements should be investigated as a diagnostic tool to identify women who may have IUI and a potential fetal compromise, as cases with preterm labor and/or preterm premature rupture of membranes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)