A porous cervical mucus plug leads to preterm birth induced by experimental vaginal infection in mice.
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ABSTRACT:
SUBMITTER: Lacroix G
PROVIDER: S-EPMC9218384 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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A porous cervical mucus plug leads to preterm birth induced by experimental vaginal infection in mice.
Lacroix Guillaume G Gouyer Valérie V Rocher Mylène M Gottrand Frédéric F Desseyn Jean-Luc JL
iScience 20220603 7
During gestation, the cervical mucus plug (CMP) acts to seal the cervical canal. Pilot studies in humans have suggested that a porous CMP may increase the risk of uterine infection and preterm birth. We examined the gel-forming content of the mouse vagina and the CMP. We experimentally infected pregnant mice by intravaginal administration of pathogens related to preterm birth in humans. We found that the epithelium in both the vagina and cervical canal of pregnant mice produced the two gel-formi ...[more]
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Project description:The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.
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Project description:Previous studies have investigated the associations between the vaginal microbiome and preterm birth, with the aim of determining whether differences in community patterns meaningfully alter risk and could therefore be the target of intervention. We report on vaginal microbial analysis of a nested case-control subset of the Pregnancy, Infection, and Nutrition (PIN) Study, including 464 White women (375 term birth and 89 spontaneous preterm birth, sPTB) and 360 Black women (276 term birth and 84 sPTB). We found that the microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners, and lower abundance of Lactobacillus crispatus. However, among women who douche, there were no significant differences in microbiome by race. The sPTB-associated microbiome exhibited a lower abundance of L. crispatus, while alpha diversity and L. iners were not significantly associated with sPTB. For each order of magnitude increase in the normalized relative abundance of L. crispatus, multivariable adjusted odds of sPTB decreased by approximately 20% (odds ratio, 0.81; 95% confidence interval, 0.70, 0.94). When we considered the impact of douching, associations between the microbiome and sPTB were limited to women who do not douche. We also observed strong intercorrelations between a range of maternal factors, including poverty, education, marital status, age, douching, and race, with microbiome effect sizes in the range of 1.8 to 5.2% in univariate models. Therefore, race may simply be a proxy for other socially driven factors that differentiate microbiome community structures. Future work will continue to refine reliable microbial biomarkers for preterm birth across diverse cohorts. IMPORTANCE Approximately 10% of all pregnancies in the United States end in preterm birth, and over 14% of pregnancies end in preterm birth among Black women. Knowledge on the associations between vaginal microbiome and preterm birth is important for understanding the potential cause and assessing risk of preterm birth. Our study is one of the largest studies performed to date to investigate the associations between vaginal microbiome and spontaneous preterm birth (sPTB), with stratified design for Black and White women. We found that the vaginal microbiome was different between Black and White women. The vaginal microbiome was associated with sPTB, and a lower abundance of L. crispatus increased the risk of sPTB independent of racial differences in microbial community structures. Furthermore, we also found that vaginal douching obscured the associations between vaginal microbiome, race, and preterm birth, suggesting that vaginal douching is an important factor to consider in future studies.
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Project description:BackgroundDespite decades of attempts to link infectious agents to preterm birth, an exact causative microbe or community of microbes remains elusive. Nonculture 16S ribosomal RNA gene sequencing suggests important racial differences and pregnancy specific changes in the vaginal microbial communities. A recent study examining the association of the vaginal microbiome and preterm birth documented important findings but was performed in a predominantly white cohort. Given the important racial differences in bacterial communities within the vagina as well as persistent racial disparities in preterm birth, it is important to examine cohorts with varied demographic compositions.ObjectiveTo characterize vaginal microbial community characteristics in a large, predominantly African-American, longitudinal cohort of pregnant women and test whether particular vaginal microbial community characteristics are associated with the risk for subsequent preterm birth.Study designThis is a nested case-control study within a prospective cohort study of women with singleton pregnancies, not on supplemental progesterone, and without cervical cerclage in situ. Serial mid-vaginal swabs were obtained by speculum exam at their routine prenatal visits. Sequencing of the V1V3 region of the 16S rRNA gene was performed on the Roche 454 platform. Alpha diversity community characteristics including richness, Shannon diversity, and evenness as well as beta diversity metrics including Bray Curtis Dissimilarity and specific taxon abundance were compared longitudinally in women who delivered preterm to those who delivered at term.ResultsA total of 77 subjects contributed 149 vaginal swabs longitudinally across pregnancy. Participants were predominantly African-American (69%) and had a preterm birth rate of 31%. In subjects with subsequent term delivery, the vaginal microbiome demonstrated stable community richness and Shannon diversity, whereas subjects with subsequent preterm delivery had significantly decreased vaginal richness, diversity, and evenness during pregnancy (P < .01). This change occurred between the first and second trimesters. Within-subject comparisons across pregnancy showed that preterm birth is associated with increased vaginal microbiome instability compared to term birth. No distinct taxa were associated with preterm birth.ConclusionIn a predominantly African-American population, a significant decrease of vaginal microbial community richness and diversity is associated with preterm birth. The timing of this suppression appears early in pregnancy, between the first and second trimesters, suggesting that early gestation may be an ecologically important time for events that ordain subsequent term and preterm birth outcomes.
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Project description:BackgroundPreterm birth is a major health problem and contributes to more than 50% of the overall perinatal mortality. Preterm birth has multiple risk factors including cervical incompetence and multiple pregnancy. Different management strategies have been tried to prevent preterm birth, including cervical cerclage. Cervical cerclage is an invasive technique that needs anaesthesia and may be associated with complications. Moreover, there is still controversy regarding the efficacy and the group of patients that could benefit from this operation. Cervical pessary has been tried as a simple, non-invasive alternative that might replace the above invasive cervical stitch operation to prevent preterm birth.ObjectivesTo evaluate the efficacy of cervical pessary for the prevention of preterm birth in women with risk factors for cervical incompetence.Search methodsWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 September 2012), Current Controlled Trials and the Australian New Zealand Clinical Trials Registry (1 September 2012).Selection criteriaWe selected all published and unpublished randomised clinical trials comparing the use of cervical pessary with cervical cerclage or expectant management for prevention of preterm birth. We did not include quasi-randomised trials. Cluster-randomised or cross-over trials were not eligible for inclusion.Data collection and analysisTwo review authors independently assessed trials for inclusion.Main resultsThe review included one randomised controlled trial. The study included 385 pregnant women with a short cervix of 25 mm or less who were between 18 to 22 weeks of pregnancy. The use of cervical pessary (192 women) was associated with a statistically significantly decrease in the incidence of spontaneous preterm birth less than 37 weeks' gestation compared with expectant management (22% versus 59 %; respectively, risk ratio (RR) 0.36, 95% confidence interval (CI) 0.27 to 0.49). Spontaneous preterm birth before 34 weeks was statistically significantly reduced in the pessary group (6% and 27% respectively, RR 0.24; 95% CI 0.13 to 0.43). Mean gestational age at delivery was 37.7 + 2 weeks in the pessary group and 34.9 + 4 weeks in the expectant group. Women in the pessary group used less tocolytics (RR 0.63; 95% CI 0.50 to 0.81) and corticosteroids (RR 0.66; 95% CI 0.54 to 0.81) than the expectant group. Vaginal discharge was more common in the pessary group (RR 2.18; 95% CI 1.87 to 2.54). Among the pessary group, 27 women needed pessary repositioning without removal and there was one case of pessary removal. Ninety-five per cent of women in the pessary group would recommend this intervention to other people. Neonatal paediatric care admission was reduced in the pessary group in comparison to the expectant group (RR 0.17; 95% CI 0.07 to 0.42).Authors' conclusionsThe review included only one well-designed randomised clinical trial that showed beneficial effect of cervical pessary in reducing preterm birth in women with a short cervix. There is a need for more trials in different settings (developed and developing countries), and with different risk factors including multiple pregnancy.
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Project description:Spontaneous preterm birth remains the leading cause of neonatal morbidity and mortality worldwide, and accounts for a significant global health burden. Several obstetric strategies to screen for spontaneous preterm delivery, such as cervical length and fetal fibronectin measurement, have emerged. However, the effectiveness of these strategies relies on their ability to accurately predict those pregnancies at increased risk for spontaneous preterm birth (SPTB). Transvaginal cervical shortening is predictive of preterm birth and when coupled with appropriate preterm birth prevention strategies, has been associated with reductions in SPTB in asymptomatic women with a singleton gestation. The use of qualitative fetal fibronectin may be useful in conjunction with cervical length assessment in women with acute preterm labor symptoms, but data supporting its clinical utility remain limited. As both cervical length and qualitative fetal fibronectin have limited capacity to predict preterm birth, further studies are needed to investigate other potential screening modalities.
| S-EPMC6033518 | biostudies-other
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