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A short cervix in the second trimester of pregnancy is a risk factor for preterm birth (PTB). Vaginal progesterone reduces this risk in specific patient cohorts. In a group of women at high risk of PTB (n=161) we examined the relationship between second trimester vaginal microbiome using 16S rRNA gene sequencing and subsequent preterm (<34 weeks, n=34) or term (>37 weeks, n=127) delivery. Additionally we assessed the effect of vaginal progesterone therapy on the vaginal microbiota. Lactobacillus iners dominance at 16 weeks was shown to be significantly associated with both a short cervix <25mm (P<0.05), and PTB <34+0 weeks (P<0.01; 69% PPV). In contrast, L. crispatus dominance was highly predictive of term birth (98% PPV). Cervical shortening or PTB were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbial structure at <18, 22, 28 and 34 weeks in women receiving vaginal progesterone (400mg/OD, n=42) or controls (n=25) showed that progesterone does not alter the vaginal microbiome and is not associated with a reduction of L. iners-associated early PTB (<34 weeks). In summary, Lactobacillus iners dominance of the vaginal microbiome at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not reduce the risk of PTB through effects upon the vaginal microbiome. |