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20: First trimester maternal serum biomarkers for prediction of preeclampsia

      Objective

      We conducted a systematic analysis of the maternal first trimester serum proteome to identify predictors of preeclampsia (PE).

      Study design

      A total of 110 women from a prospective observational cohort were included in this study. Maternal serum samples were collected between 9 and 11 gestational weeks. PE was defined as mild or severe following ACOG classification. Maternal serum proteome analysis was performed by fluorescence 2 D gel analysis, multidimensional liquid chromatography tandem mass spectrometry and label-free quantification. Pair-wise comparison was performed by x2 goodness-of-fit tests and adjusted for multiple comparisons via the false-discovery rate method. Immunoassays were used for accurate quantification and evaluated by the Receiver Operating Characteristic (ROC) curves and logistic regression analysis.

      Results

      Control group comprised 44 women who delivered at term, 21 subjects developed mild PE at 36 weeks gestation (mean) and 45 severe PE at 31 weeks gestation (mean). There were no significant differences in demographic or reproductive factors between the groups. Proteome analysis revealed 416 unique proteins for label-free quantification including 24 differentially expressed (p<.05) in PE. Differentially expressed proteins included immunoregulators (Lipopolysaccharide-binding protein), cytoskeletal proteins (Tubulin beta, Filamin), vascular and lipid metabolism proteins (Vascular cell adhesion protein, Vasorin, Cathepsin D, Apolioprotein A II) and extracellular matrix proteins. Immunoassay for 5 potential biomarkers demonstrated discriminant capability with AUROCs ranging from 0.66 to 0.89. Logistic Regression analysis showed positive interaction and increased the discriminant ability (AUROC>0.80). Serum markers of active PE such as fibronectin, S-endoglin and VEGFRs were not significant in this analysis.

      Conclusion

      First trimester maternal serum proteome analyses identified a distinct set of positive predictors of PE. This may provide a sensitive maternal serum test to predict PE in first trimester and facilitate early intervention.