Amniotic fluid proteomic signatures of cervical insufficiency and their association with length of latency.

Abstract

Cervical insufficiency is a precursor of preterm birth. Treatment with emergency cervical cerclage is contraindicated in the presence of intra-amniotic infection. Detecting infection with Gram stain and culture of amniotic fluid lacks sensitivity. Proteomic profiling of amniotic fluid in cervical insufficiency may help identify pregnancies best suited for emergency cerclage. Thirty-two pregnant women underwent amniocentesis for routine genetic testing (n=22) or after diagnosis of cervical insufficiency (n=10). The proteomic profiles of the amniotic fluid samples were compared in a cross-sectional fashion, including sub-analyses of women with cervical insufficiency and latency periods of <1week and >1week post-diagnosis. Mean gestational age at diagnosis of cervical insufficiency was 21.4weeks (95% CI 20.6-22.1). Proteomic analysis yielded 40 (7.2%, P<0.05) differentially expressed proteins between women with delivery <1week (n=6) vs. >1week (n=4). Women who delivered <1week had activated inflammatory response (z=2.3, P=6.71E-09), chemotaxis of immune cells (z=2.9, P=2.01E-08), and inhibited bacterial growth (z=-2.2, P=5.82E-05). A multivariate model of eight biomarkers positively associated with cases of <1week latency and distinguished cases from controls (97.8%, cross-validation accuracy 92.7%, P=0.0009). In this pilot study, significant differences in the amniotic fluid proteomic profiles in cases of cervical insufficiency compared to genetic amniocentesis were observed. Proteomic signatures were predictive of achieving latency > 1week after diagnosis of cervical insufficiency. These preliminary findings suggest that proteomic analysis may be of value in predicting outcome following cervical insufficiency and warrants further validation in larger studies.