Prediction of preterm birth in twin gestations through analysis of maternal plasma at 24-30 weeks gestation

OBJECTIVE: The majority of morbidity and mortality in twins occurs with delivery 34 wk. STUDY DESIGN: Secondary analysis of maternal plasma samples from an RCT of 17 α-hydroxyprogesterone caproate in twins and triplets. Samples obtained at randomization from twins in the placebo group with PTB 34 wk (Group 2,N=7), matched by maternal age, ethnicity, and gestational age at sample collection were compared. Differentially expressed proteins were identified by multidimensional liquid chromatography- tandem mass spectrometry (LC/LC-MS/MS). Pair-wise comparison was performed using χ2 goodness-of-fit tests and a pvalue <0.05 was considered significant. Fold-change between the 2 groups was determined after differential candidates passed the calculated Z-score thresholds. RESULTS: 29 proteins were significantly differentially expressed between the groups (p <0.05). Of those, 15 were overexpressed in Group 1 (PTB<34) compared with Group 2. Overexpressed proteins of interest included 5 cell-cell adhesion proteins (Ficolin-3, Gelsolin, Tenascin-X, Galectin-3-binding protein, and Insulin-like growth factor- binding protein complex acid liable subunit). Expression of Profilin- 1 and Plastin-2 was two-fold higher in Group 2 than Group 1 although these differences did not reach statistical significance. Cellular Fibronectin was not different between groups. CONCLUSION: Increased maternal plasma levels of cell-cell adhesion proteins are associated with subsequent PTB <34 wk in twin gestations, confirming our earlier findings in CVF. These include both positive (Ficolin-3 and Gelsolin) and negatively associated (Profilin- 1) proteins that are distinct from markers of recurrent PTB in singletons.