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Proteomic biomarker sets identify synergistic pathways that predict the outcome of rescue cerclage (RC)

      Objective

      The origin of incompetent cervix is multifactorial, and the success of RC unpredictable. Intra-amniotic inflammation complicates 25% of pregnancies undergoing RC, and its presence predicts failure. An intra-amniotic proteomic inflammatory profile was described by SELDI (mass restricted: MR Score). We report here a new independent biomarker predictive of cerclage failure whose impact is synergistic with a + MR.

      Study design

      Amniocentesis was performed to facilitate RC in 37 consecutive women with painless dilation (>2 cm) and no detectable uterine activity. 39 consecutive women with a sonographically normal pregnancy and cervix undergoing amniocentesis for chromosome testing provided control. A proteomic fingerprint was generated using SELDI on the discarded fluid. Peaks were sought for the 4 proteins of the MR Score (inflammation) and for hemoglobin (Hb) as evidence of decidual hemorrhage/intra-amniotic bleeding.

      Results

      Amniocentesis was performed at 23.5w in cerclage (mean dilation 4cm) vs.19.5w in control subjects. Cerclage women delivered at 28.8w, controls at 39.2w. Thirty two of 37 (86%) cerclage subjects delivered prematurely. Hb peaks were present in 12 of 37 (30%) cerclage but in no control subjects. Women with Hb peaks delivered earlier than those without (latency: − Hb: median 38 d, range 0-148 d vs. + Hb: median 6 d, range 0-100 d, P < .04; % prolongation: − Hb: median 21.8%, range 0.7-117% vs. + Hb: median 3.8%, range 0-57%, P = .03). There was no relationship between cervical dilation and presence of Hb. Women with a − MR and no Hb had a median latency of 40.5 d (range 1-148 d) vs. those with either a + MR or + Hb (but not both) whose latency was 14 d (range 0-105 d) vs. those with both a + MR and + Hb whose latency was 3 d (range 0-43 d).

      Conclusion

      These findings illustrate a second pathologic mechanism, presumably decidual bleeding which like inflammation is associated with cervical ripening independent of uterine contractions. The negative controls demonstrate the bleeding occurs pre cerclage. The presence of either predicts cerclage failure with synergism.