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11: Maternal serum biomarkers of gestational hypertension distinct from preeclampsia

      Objective

      To characterize the maternal serum proteome profile in gestational hypertension (GH).

      Study Design

      . A total of 130 women from a prospective observational cohort were included in this study. Maternal serum samples were collected between 21 and 37 gestational weeks. GH and preeclampsia (PE) were classified by Working Group criteria (Am J Obstet Gynecol 2000;183). Maternal serum proteome analysis was performed using multidimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) and label-free quantification (spectral counting). Pair-wise comparison was performed using χ2 goodness-of-fit tests and adjusted for multiple comparisons via the false-discovery rate (FDR) method. Immunoassays were used for accurate quantification and evaluated using the Receiver Operating Characteristic (ROC) curves and logistic regression analysis.

      Results

      14 women developed GH at a mean of 32 weeks gestation, 29 developed mild PE (mean 35 weeks), 29 developed severe PE (mean 31 weeks), and 58 remained normotensive and delivered at term. 2D-LC-MS-MS analysis of maternal sera identified 480 unique proteins for label-free quantification. Cluster analysis showed a unique cluster of proteins differentially expressed in GH distinct from mild and severe PE. Label-free quantification identified 36 differentially expressed (p<0.05) proteins between patients with GH compared to PE. These included cytoskelatal proteins (talin, filamin A, tropomyosin alpha, actin aortic smooth muscle); placental proteins (PAPPA-2, HCG); and matrix proteins. Analysis of 17 potential biomarkers with specific immunoassays showed good discriminating capability between GH and PE (AUROC′s 0.73 to 0.82). Multi-analyte analysis showed further increased the discriminant ability (AUROC>0.88).

      Conclusion

      Systematic and comprehensive maternal serum proteome analyses identified a multi-analyte panel of serum biomarkers for GH. Reliable diagnosis of GH that could distinguish from PE could facilitate early and specific intervention strategies.