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13: Iimproved sensitivity (SEN) & positive predictive value (PPV) for the detection of pre-term labor (PTL): A new multivariate quantitative protein microarray serum panel

      Objective

      Interventions for PTL have been very unsuccessful in part because of inadequate identification of candidates for therapy. Available markers have high negative predictive values (NPV) but poor SEN and PPV. We have investigated a new set of protein markers to achieve a much higher SEN while maintaining high specificity (SPEC) and NPV

      Study design

      Serum specimens were obtained from 318 gravidas (152 in imminent/early labor and 166 NIL). First, we used high-resolution mass spectrometry and proteome enrichment kits (the prOTOF2000TM and ProEXPRESSION Protein Fractionation kits, PerkinElmer; ProteinChip® Bio-Rad) for peptide and protein biomarkers that correctly discriminated patients for imminent labor; second, several bioinformatic platforms were then employed to discern potential markers. Third, several of the most predictive candidates called RAL 1,2,& 3 (IP in progress) were selected for sequence identification and, fourth, we then validated markers on our in-house, quantitative protein microarray platform in a panel with several other putative markers and compared with published FFN data. Specificity (SPEC) was set at 95%+ for PBEF and multivariate analyses.

      Results

      Components PBEF, RAL 1,2,3, both in univariate analyses and multivariate analysis showed much higher SEN and PPV for PT than FFN.

      Conclusion

      PBEF, per se, and RAL 1,2,& 3 in univariate and multivariate combinations produce dramatically higher SEN and PPV for similar SPEC and NPV to FFN (IOM report 2006). Accurate identification of pts at imminent high risk may allow for targeted interventions to reduce the sequelae of pre-term birth without requiring unnecessary, expensive treatment of large numbers of low risk patients. Serum testing also has considerable advantages over cervical swabs.
      Tabled 1Multivariate quantitative protein microarray serum panel
      SENSSPECPPVNPV
      RAL Multivar88%95%72%98%
      PBEF39%96%75%98%
      RAL 181%84%40%97%
      RAL 278%77%32%91%
      RAL 383%77%33%97%
      FFN (IOM)39%95%30%92%