Maternal Azithromycin therapy for Ureaplasma parvum intra-amniotic infection improves fetal hemodynamics in a non-human primate model.

BACKGROUND: Ureaplasma parvum infection is a prevalent cause of intrauterine infection that is associated with preterm birth, preterm premature rupture of membranes, the 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 assesses the effect of intra-amniotic Ureaplasma infection on fetal hemodynamic and cardiac function and the impact of maternal antibiotic treatment on these outcomes. STUDY DESIGN: Chronically catheterized pregnant rhesus monkeys were assigned to control (n=6), intra-amniotic inoculation with Ureaplasma parvum (10(7) CFU/ml, IAI, n=15); and intra-amniotic infection plus Azithromycin treatment (12.5 mg/kg BID I.V., IAI+AZI, n=8) groups. At approximately 135days gestation (term=165 days), pulsed and color Doppler ultrasonography was utilized to obtain measurements of fetal hemodynamics (pulsatility index of umbilical artery, ductus venosus, descending aorta, ductus arteriosus, aortic isthmus, right pulmonary artery, middle cerebral artery and cerebro-placental ratio, and left and right ventricular cardiac outputs) and cardiac function (E/A ratio, Tei index). These indices were stratified by amniotic fluid pro-inflammatory mediator levels and cardiac histology. RESULTS: Umbilical and fetal pulmonary artery vascular impedances were significantly increased in IAI animals (p 1.1) than those with normal blood flow (p 1.6, p<0.05). Amniotic fluid IL-6 concentrations were elevated in cases of abnormal RCO/LCO ratio compared to normal cases (p<0.05). CONCLUSIONS: Fetal hemodynamic alterations were associated with intra-amniotic Ureaplasma infection and ameliorated following maternal antibiotic treatment. Doppler ultrasonographic measurements merit continuing investigation as a diagnostic method to identify fetal cardiovascular and hemodynamic compromise associated with intrauterine infection or inflammation, and in the evaluation of therapeutic interventions or clinical management of preterm labor.