The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk

Abstract

BackgroundPreterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix.Results Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix <25 mm (n = 15, P < 0.05) and preterm birth <34+0 weeks (n = 18; P < 0.01; 69% PPV). In contrast, Lactobacillus crispatus dominance was highly predictive of term birth (n = 127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28, and 34 weeks) was then undertaken in women receiving vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks).Conclusions L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about “infection risk” associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0223-9) contains supplementary material, which is available to authorized users.

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

“…Comparison with Kindinger et al A recent study also examined the relationship between the vaginal microbiota and PTB in a similarly sized cohort (n = 161) of predominantly Caucasian and Asian women with a prior history of PTB (37). Using a CSTbased analysis, they corroborated an association between increased gestational frequency of L. crispatus and reduced risk for PTB.…”

“…Some but not all Lactobacillus species can produce lactocillin, a peptide possessing potent antibiotic activity against G. vaginalis and other Gram-positive pathogens (36). Although some evidence suggests that L. iners may contribute to adverse health outcomes (37), it would be consistent with our findings, and previous observations that the L. iners-dominated CST3 is relatively unstable (11,32), if L. iners were itself harmless but promoted or at least did not inhibit the growth of other harmful microbes.…”

Maternal microbiomes in preterm birth: Recent progress and analytical pipelines

“…Kits such as the QIAamp DNA Stool Mini Kit (QIAgen) 14,21,24,45 , are used to extract microbial DNA from primarily from stool, but have been used to isolate microbial DNA from other human niches. However, since DNA extraction kits that target low abundance microbial communities like the placenta are not yet available, investigators have used kits such as the DNeasy PowerSoil Kit (MOBIO) 42,44 , which can capture DNA from a variety of biological sources.…”

“…Thus, more and more studies are beginning to address how microbes inhabiting this particular niche contribute to the PTB outcome. During the 2 nd trimester of pregnancy, in women with a short cervix the preponderance of specific Lactobacillus species correlates with the gestational age at delivery—where increased vaginal L. iners is associated with preterm birth and L. crispatus is associated with term birth 24 . Further, the administration of vaginal progesterone, which normally used as a therapeutic for delaying early delivery, does not alter the vaginal microbiota 24 .…”

“…During the 2 nd trimester of pregnancy, in women with a short cervix the preponderance of specific Lactobacillus species correlates with the gestational age at delivery—where increased vaginal L. iners is associated with preterm birth and L. crispatus is associated with term birth 24 . Further, the administration of vaginal progesterone, which normally used as a therapeutic for delaying early delivery, does not alter the vaginal microbiota 24 . Recently, Ghartey et al analyzed metabolites in the cervicovaginal fluid at two time points in women who went on to deliver either preterm or at term and identified several that differed between the two groups 25 .…”