Non-invasive prediction of preterm birth in women with cervical insufficiency or an asymptomatic short cervix (≤25 mm) by measurement of biomarkers in the cervicovaginal fluid

OBJECTIVE: To determine whether various proteins in the cervicovaginal fluid (CVF) known to be involved in immune regulation, alone or in combination with clinical risk factors, can predict spontaneous preterm delivery (SPTD) in women with cervical insufficiency or a short cervix (≤25 mm). METHODS: This retrospective cohort study included 62 asymptomatic women with cervical insufficiency (n = 27) or an asymptomatic short cervix (n = 35) at 18–27 weeks. CVF swab samples were taken for assays of vitamin D binding protein (VDBP), interleukin (IL)-8, matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and Dickkopf-related protein 3 (DKK3) before cervical examination, and maternal blood was collected for the determination of the C-reactive protein (CRP) level. The primary outcome measurement was SPTD at <32 weeks of gestation. Logistic regression analysis and receiver operating characteristic curves were used for the statistical analyses. RESULTS: The rate of SPTD at <32 weeks was 40.3% (25/62). The CVF levels of VDBP, TIMP-1, and DKK3, but not IL-8 and MMP-9, were significantly higher in the women who had SPTD at <32 weeks than in those who did not deliver spontaneously at <32 weeks. The women who had SPTD at <32 weeks had a significantly more advanced cervical dilatation at presentation and a higher level of serum CRP. Using the stepwise regression analysis, a prediction model was developed by combining various proteins in the CVF and clinical factors, resulting in the inclusion of cervical dilatation, CVF VDBP, and use of corticosteroids (area under curve, 0.909). CONCLUSIONS: In women with cervical insufficiency or a short cervix, VDBP, TIMP-1, and DKK3 in the CVF may be useful as non-invasive predictors of SPTD at <32 weeks. A combination of these markers and clinical factors appears to improve the predictability of SPTD compared with the markers alone.