10: Distinct microbiota in the cervicovaginal space are associated with spontaneous preterm birth: findings from a large cohort and validation study


      Changes in microbial communities have been implicated in both health and disease. Investigations into the association between the cervicovaginal (CV) microbiota and spontaneous preterm birth (SPTB) have been limited in scope and number. This study sought to assess if longitudinal cohort of pregnant women and then to perform validation in a 2nd prospective cohort.

      Study Design

      A prospective cohort of singleton pregnancies were enrolled (“M&M”, n=1500). Biospecimens were collected at 3 time points in pregnancy (16-20 (V1), 20-24 (V2), 24-28 (V3) weeks). All cases of PTB were adjudicated by the PI. From the larger cohort, a nested case-control was performed with 80 SPTB cases and 320 term controls that were frequency matched by race to the cases. 16S rRNA gene analyses were performed to characterize the composition and structure of the CV microbiota. The effect of bacteria was quantified as the log ratio between the mean relative abundance at SPTB samples vs. TERM delivery samples. The log ratios were estimated using zero-inflated negative binomial models. A second cohort of woman (“STOP”) with specimens collected between 22-32 weeks was used as validation (N=616).


      When performing phylotype analyses, 127 phylotypes were detected in all samples from both cohorts. Significant associations were demonstrated between specific bacteria, in both a positive and negative manner, with SPTB. 37 bacteria were significantly associated with a decreased risk of SPTB while 13 were associated with an increased risk in the primary cohort. Racial differences in these associations were evident (figure 1). The validation cohort confirmed the highly significant associations between specific microbes and SPTB. Bifidobacterium species were noted to be significantly protective against SPTB at all gestational time points while BVAB2, BVAB3 and Mobiluncus were associated with a dramatic increase risk of SPTB (all q-values <0.0001).


      CV microbiota are significantly associated with SPTB. Targeting the bacteria that are associated with an increased risk of SPTB and/or enhancing the presence of the protective bacteria may serve as new therapies to reduce the rate of PTB. With this new evidence, these types of studies should become a research priority. (R01NR014784).
      Figure thumbnail fx1