OBJECTIVE-To characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta or percreta shares features of epitehelial-mesenchymal-transition (EMT).STUDY DESIGN-We analyzed gestational age matched serum samples from 90 pregnant women with either complete placenta previa (n=45) or uncomplicated pregnancies (n=45). Vascular-endothelial-growth-factor (VEGF), placental-growth-factor (PlGF) and soluble fms-liketyrosine-kinase-1 (sFlt-1) were immunoassayed. VEGF and phosphotyrosine (P-Tyr) immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. RESULTS-Women Disclosure statement:The authors have nothing to disclose CONTRIBUTIONS TO AUTHORSHIP MJW, EF, IAB and CSB formulated the hypothesis, designed the study, collected, analyzed, and interpreted the data and drafted the manuscript. MJW and CSB recruited patients and together with ST, MOB, EW, KC, AKS and CL collected biological specimens and followed the patients prospectively to the point of delivery. MJW and GZ conducted the ELISA assays and the immunohistochemistry experiments. IAB, MJW, CSB and CMS evaluated and performed the histological analysis of our specimens. All the co-authors participated with aspects of study design, critical interpretation of the data, contributed to writing of the paper and have reviewed and approved the final version. NIH Public Access Author ManuscriptAm J Obstet Gynecol. Author manuscript; available in PMC 2012 May 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript CONCLUSIONS-Lower systemic free VEGF and a switch of the interstitial EVT to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.

Introduction Intra-uterine infection is a global problem and a significant contributor to morbidity and perinatal death. The host response to infection causes an inflammatory state that acts synergistically with microbial insult to induce preterm birth and fetal damage. Prompt and accurate diagnosis of intra-amniotic infection in the asymptomatic stage of the disease is critical for improved maternal and neonatal outcomes. Areas Covered This article provides an overview of the most recent progress, challenges and opportunities for discovery and clinical implementation of various maternal serum, cervico-vaginal and amniotic fluid biomarkers in pregnancies complicated by intra-amniotic infection. Expert Opinion Clinically relevant biomarkers are critical to the accurate diagnostic of intra-uterine infection. Front end implementation of such biomarkers will also translate in lower incidence of early-onset neonatal sepsis which is an important determinant of neonatal morbidity and mortality associated with prematurity. However, of the hundreds of differentially expressed proteins, only few may have clinical utility and thus function as biomarkers. The small number of validation studies along with barriers to implementation of technological innovations in the clinical setting are current limitations.

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