Proteomic biomarkers that predict the clinical success of rescue cerclage
The origin of incompetent cervix is multifactorial, and the success of rescue cerclage is unpredictable. We tested amniotic fluid from women who were preparing to undergo rescue cerclage for proteomic biomarkers and correlated their presence with clinical outcome. Amniocentesis was performed to facilitate rescue cerclage in 37 consecutive women with painless dilation (> 2 cm) and no detectable uterine activity for 4 hours (range, 1-24 hours) before cerclage. Thirty-nine consecutive women with a sonographically normal pregnancy and cervix who underwent amniocentesis for chromosomal testing during the same study interval at the same clinical site provided the control samples. A proteomic fingerprint was generated with the discarded sample and the Mass-Restricted score (MR score) for inflammation calculated. Peaks corresponding to free hemoglobin chains were sought as evidence of decidual hemorrhage or intra-amniotic bleeding. Amniocentesis was performed at 23.5 weeks in cerclage (mean dilation, 4 cm) versus 19.5 weeks in control subjects. Cerclage subjects were delivered at 28.8 weeks; control subjects were delivered at 39.2 weeks. Thirty-two of 37 of cerclage subjects (86%) were delivered prematurely. Ten of 37 of cerclage subjects (27%), but no control subject, had a MR score that was indicative of inflammation (P < .001). Hemoglobin peaks were present in 12 of 37 of cerclage subject (32%), but no control subjects. Among cerclage subjects, those with a MR score of 3 to 4 were delivered earlier than those with a MR score of 0 to 2 (P < .001). Women with a MR score of 3 to 4 had a shorter latency period (days from amniocentesis to delivery; 3 days) and a shorter percentage of prolongation (1.8%) than women with a MR score of 0 to 2 (35 days; P < .05; 17.9%; P < .05). Women with hemoglobin had a shorter latency period (6 days) and a shorter percentage of prolongation (3.8%) than women without hemoglobin (38 days; P < .05; 21.8%; P < .05). Hemoglobin was present in 7 of 10 of the cerclage subjects (70%) with a MR score of 3 to 4. Women with both a MR score of 3 to 4 and hemoglobin had the shortest intervals to delivery. These findings illustrate 2 pathologic mechanisms that are associated with preterm delivery are also associated with incompetent cervix. Either an intrauterine inflammatory response or decidual hemorrhage predates surgery in one half the women whose condition requires rescue cerclage. The activation of either mechanism predicts cerclage failure.