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AMONG WOMEN IN PRETERM LABOR PETER ROBILIO, JANE HITTI, JODI LAPIDUS, XINFANG LU, LEONARDO PEREIRA, MICHAEL GRAVETT, SRINIVASA NAGALLA, University of Washington, Seattle, Washington, Oregon Health & Science University, Portland, Oregon, ProteoGenix, Inc., Beaverton, Oregon OBJECTIVE: To identify potential serum biomarkers to predict spontaneous preterm birth (SPTB) from women in preterm labor by a systematic analysis of the maternal serum proteome. STUDY DESIGN: This is a secondary analysis of archived serum samples collected prospectively from 138 women in spontaneous preterm labor at 20-34 weeks gestation at the University of Washington. SPTB was defined as spontaneous delivery 34 weeks. Women diagnosed with intra-amniotic infection were excluded. Sera were immunodepleted for high abundance proteins and analyzed using fluorescence 2D gel analysis, multidimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), and label-free quantification (spectral counting). Pair-wise comparison was performed using 2 goodness-of-fit tests. Statistical significance was determined after adjusting for multiple comparisons. Immunodetection was used to confirm potential candidate biomarkers. RESULTS: Of 138 subjects, 59 (43%) delivered at 34 weeks (SPTB), while 79 (57%) subjects delivered at term (PTL, term group). There were no significant differences in demographic or reproductive factors between SPTB and PTL term groups. A total of 369 unique serum proteins were identified for label-free quantification. Twenty six proteins were differentially expressed (p 0.05) between PTL and SPTB samples. The majority of these proteins are produced in the placenta or decidua and included immunoregulatory, transport, and extracellular matrix proteins. CONCLUSION: Proteomic analysis identified multiple maternal serum biomarkers that accurately discriminated SPTB from labor without delivery. This may facilitate diagnosis of women in preterm labor destined for delivery from those in false labor and lead to targeted early therapy. |