Neutrophil defensins but not interleukin-6 in vaginal fluid after preterm premature rupture of membranes predict fetal/neonatal inflammation and infant neurological impairment

Objective. To determine whether neutrophil defensins (HNP1-3) and interleukin-6 (IL-6) in vaginal fluid after preterm premature rupture of membranes predict fetal inflammatory response syndrome (FIRS), neurological impairment or chorioamnionitis. Design. Prospective study. Setting. Tertiary referral university hospital. Population. Forty-two patients with preterm premature rupture of membranes at <32 weeks. Methods. Levels of HNP1-3 and IL-6 were measured in vaginal fluid obtained by swabs. Mann Whitney U-test was used to compare HNP1-3 and IL-6 levels in groups with vs. without FIRS, infant death or neurological impairment, and chorioamnionitis (p<0.05 significant). Logistic regression was used to control for potential confounders. Diagnostic accuracies of HNP1-3 and IL-6 were determined by receiver operator characteristics analysis. Main Outcome Measures. Fetal inflammatory response syndrome was defined as neonatal inflammation within 72hours postpartum. Neurological impairment was defined as motor and/or tone abnormalities at one year of corrected age. Chorioamnionitis was diagnosed histologically. Results. Levels of HNP1-3, but not IL-6, were higher in 12 cases of FIRS (p=0.019 and p=0.256, respectively). Levels of HNP1-3, but not IL-6, were higher in 14 cases of infant death or neurological impairment (p=0.015 and p=0.100, respectively) and, when only survivors were analyzed, in nine cases of neurological impairment (p=0.030 and p=0.187, respectively). Levels of HNP1-3 and IL-6 were higher in 29 cases of chorioamnionitis (p=0.005 and p=0.003, respectively). The differences remained significant after adjustment for gestational age. Levels of HNP1-3 predicted FIRS, infant death or neurological impairment and chorioamnionitis with an area under the curve of 0.75, 0.79 and 0.78, respectively. Conclusions. Elevated vaginal fluid HNP1-3 and IL-6 levels are associated with histological chorioamnionitis. Elevated HNP1-3 can also identify FIRS and predict infant death or neurological impairment.