PROGNOSTIC AND DIAGNOSTIC MONITORING OF MATERNAL-FETAL HEALTH SRINIVASA NAGALLA, MICHAEL GRAVETT, LEONARDO PEREIRA, JANE HITTI, DAVID ESCHENBACH, BO JACOBSSON, JUHA RASANEN, DAVID LUTHY, Oregon Health & Science University, Pediatrics, Portland, Oregon, University of Washington, Obstetrics & Gynecology, Seattle, Washington, Oregon Health & Science University, Obstetrics and Gynecology, Portland, Oregon, University of Washington, Obstetrics and Gynecology, Seattle, Washington, Gothenborg University, Goteborg, Sweden, University of Oulu, Obstetrics and Gynecology, Oulu, Finland, Obstetrix Medical Group, Seattle, Washington OBJECTIVE: To perform comprehensive proteomic analyses of the amniotic fluid (AF), cervico-vaginal fluid (CVF), umbilical cord serum (FS) and maternal serum (MS) proteomes and evaluation of the potential value of proteome profiles to diagnose intra-amniotic infection (IAI), spontaneous preterm birth (SPTB) and pre-eclampsia (PE). STUDY DESIGN: Samples from 3 prospective cohorts (IAI, SPTB, PE, n=724) were chosen for multiple proteomic analyses including, 2-dimensional (2D) gel electrophoresis, 2D liquid chromatofocussing, multidimensional liquid chromatography tandem mass spectrometry and a combination of protein identification algorithms to decipher the four proteomes. Samples were purified to remove high-abundance proteins and enriched for glycoproteomes. Label-free quantification was used to assign relative abundance of each protein in the respective proteome. Pair-wise comparisons and trend analyses were used to monitor gestational age-dependent changes and to establish significance of various biomarkers for IAI, SPTB and PE. RESULTS: Protein identification revealed O500 proteins in each of the four proteomes. Comparison of w250 proteins (high score, O2 peptides for each protein) from each proteome showed overlap of AF (30%), CVF (O32%) and FS (O85%) with maternal serum. 11-13% of proteins were present in all four proteomes, while 45-52% are unique to each, and relative ranking of abundantly expressed proteins are distinct. Gestational age changes in AF and MS were greatest between the 1st and 2nd trimesters. Pair-wise comparison of control and cases of IAI, or SPTB identified 10-12 sensitive and specific biomarkers in AF and CVF. Longitudinal comparisons in PE identified a distinct protein profile potentially diagnostic in early gestation. Glycoproteome comparisons showed that hyper-glycosylation was associated with SPTB and PE. CONCLUSION: Comprehensive analysis of the AF, CVF, FS, and MS proteomes provides the foundation for systematic evaluation of prognostic and diagnostic biomarkers of pregnancy-related disorders and will provide insight into pathophysiology.