17: Determinants of pregnancy outcome in pregnant women with a short cervix

Abstract

Short cervical length in mid-gestation is a risk factor for spontaneous preterm birth (SPTB). We sought to determine whether measurement of compounds in vaginal secretions, coupled with composition of the vaginal microbiome, would improve the ability to predict which women are most at risk for SPTB. Cervical length was measured by ultrasonography in 568 women at 18-24 weeks gestation at three hospitals in Brazil. Vaginal microbiome composition was determined by analysis of the V1-V3 region of the gene coding for bacterial 16S ribosomal RNA. Quantification of the D- and L-lactic acid isomers, TIMP-1 and MMP-8 in vaginal secretions were by ELISA. Differences between women with a short or normal cervix were evaluated by mean ± SD, median (p25-p75), Kruskal-Wallis test and Mann-Whitney test. Eighty-one (14.3%) women with a cervical length ≤25 mm were compared with 487 women whose cervix was >25 mm. L. crispatus was the numerically dominant bacterium in 33.3% and 43.1% of women with a short or normal cervix, respectively. Conversely, L. iners and Gardnerella vaginalis were dominant in 38.3% and 18.5% of women with a short cervix vs. 31.0% and 10.9% of those with a cervix >25mm. The difference in G. vaginalis dominance was significant (p=0.050). Vaginal levels of TIMP-1 were highest (p=0.018) and D-lactic acid levels were lowest (p< 0.001) in women with a short cervix. In women with a short cervix, levels of TIMP-1, MMP-8 and D- and L-lactic acid differed depending on whether L. crispatus, L. iners or G. vaginalis was dominant (p< 0.007). The concentrations of TIMP-1 and MMP-8 were lowest, and D-lactic acid was highest when L. crispatus was the dominant bacterium. The mean gestational age at birth was lower in women with a short cervix compared to women with a cervical length >25mm (p=0.033) and the rate of SPTB was higher (p=0.086). The combination of low D-lactic acid and high TIMP-1 concentrations in vaginal secretions identify women with a cervix ≤25mm whose vaginal microbiome is not dominated by L. crispatus and who are at increased risk for SPTB.View Large Image Figure ViewerDownload Hi-res image Download (PPT)