481: Maternal-fetal cellular trafficking and fetal inflammation in patients with preterm premature rupture of membranes

Abstract

inflammation in patients with preterm premature rupture of membranes Dana Henry, Yvonne Cheng, Payam Saadai, Sheila Keating, Tzong-Hae Lee, Philip Norris, Michael Busch, Roberto Romero, Tippi MacKenzie UCSF, Obstetrics and Gynecology, San Francisco, CA, UCSF, Surgery, San Francisco, CA, Blood Systems Research Institute, Blood Bank, San Francisco, CA, Hutzel Women’s Hostpial, Obstetrics and Gynecology, Detroit, MI OBJECTIVE: Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells between the mother and her fetus. We previously reported alterations in trafficking after fetal surgery but the extent of MFCT in preterm premature rupture of membranes (PPROM) has not been characterized. We studied MFCT and changes in potential biomarkers in maternal and umbilical cord blood in PPROM. STUDY DESIGN: We prospectively obtained matched maternal and umbilical cord blood samples from 23 healthy term control patients and 13 patients with PPROM. The extent of MFCT was determined using PCR for non-shared HLA-DR alleles. “High traffickers” were defined as those above the 75th percentile of control patients. Serum cytokine and chemokine levels were analyzed using a human 39plex immunoassay system (Millipore). RESULTS: The gestational age at delivery was lower in patients with PPROM than in the control group (33.1 vs. 39.5 wks, p 0.01 by t-test). High trafficking of maternal cells into cord blood was more common in patients with PPROM than in those in the control group (60% vs. 23%, P 0.007 by Chi-square test), while trafficking of fetal cells in maternal blood was unchanged. Fetal levels of Flt-3 ligand, IL-1 , IL-1R , IL-10, monocyte chemotactic protein-1, and sIL-2R were significantly higher in PPROM, while levels of macrophage-derived chemokine were significantly lower (p 0.05 by Kruskal-Wallis). Maternal levels of IL-6 and IL-10 were increased and levels of eotaxin were decreased in PPROM compared to controls. Patients with PPROM and high trafficking had significantly higher concentrations of the chemokine MIP-1 (CCL4) in cord blood than those with low trafficking, suggesting a mechanism for recruitment of maternal cells. CONCLUSION: This is the first demonstration of high MFCT in PPROM, with coordinate changes in inflammatory and chemotactic cytokines in fetal blood. Our observations suggest a fetal origin of labor in PPROM and indicate potential new targets for therapeutic intervention. 482 Placental histologic findings of chorion-decidual hemorrhage and inflammation in spontaneous preterm birth influence outcomes in the subsequent pregnancy David Hackney, Radhika Tirumala, Linda Salamone, Richard Miller, Philip Katzman University of Rochester School of Medicine, Obstetrics and Gynecology, Rochester, NY, University of Rochester School of Medicine, Pathology, Rochester, NY, Rochester General Hosptial, Obstetrics and Gynecology, Rochester, NY OBJECTIVE: Spontaneous preterm birth (SPTB) is a common endpoint of different underlying etiologies, including inflammation and chorion-decidual bleeding. The presumed etiology from placental histology may influence outcomes in subsequent pregnancies. STUDY DESIGN: Included subjects had: 1) a SPTB after 2004 with available placental pathology and 2) a subsequent delivery at 20 weeks EGA at our institution. Exclusion criteria were multifetal gestation, thrombophilia, anticoagulation or substance abuse. For included subjects archived placenta and membrane paraffin blocks from the index SPTB were cut, stained with Prussian Blue and evaluated by a perinatal pathologist for the presence of hemosiderin. The association between histologic findings and subsequent pregnancy outcomes were evaluated through logistic and linear regression. RESULTS: A total of 131 subjects were included, of whom 39.7% had a recurrent SPTB. The index SPTB demonstrated chorioamnionitis in 42.7%, vasculitis or funisitis in 24.4% and chorion-decidual bleeding Unadjusted and propensity score (PS)-adjusted risk ratios (95% confidence interval) of respiratory distress syndrome (RDS) and neonatal sepsis by antenatal corticosteroid (ACS) exposure and gestational age at delivery Levels of cytokines and chemokines in umbilical cord blood of normal term control patients and those with PPROM Poster Session III Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases www.AJOG.org