Dataset Information

First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk.

ABSTRACT: Preterm birth is a leading cause of global neonate mortality. Hospitalization costs associated with preterm deliveries present a huge economic burden. Existing physical/biochemical markers for predicting preterm birth risk are mostly suited for application at mid/late pregnancy stages, thereby leaving very short time (between diagnosis and delivery) for adopting appropriate intervention strategies. Recent studies indicating correlations between pre/full-term delivery and the composition of vaginal microbiota in pregnant women have opened new diagnostic possibilities. In this study, we performed a thorough meta-analysis of vaginal microbiome datasets to evaluate the utility of popular diversity and inequality measures for predicting, at an early stage, the risk of preterm delivery. Results indicate significant differences (in diversity measures) between 'first-trimester' vaginal microbiomes obtained from women with term and preterm outcomes, indicating the potential diagnostic utility of these measures. In this context, we introduce a novel diversity metric that has significantly better diagnostic ability as compared to established diversity measures. The metric enables 'early' and highly accurate prediction of preterm delivery outcomes, and can potentially be deployed in clinical settings for preterm birth risk-assessment. Our findings have potentially far reaching implications in the fight against neonatal deaths due to preterm birth.

SUBMITTER: Haque MM

PROVIDER: S-EPMC5700938 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk.

Haque Mohammed Monzoorul MM Merchant Mitali M Kumar Pinna Nishal PN Dutta Anirban A Mande Sharmila S SS

Scientific reports 20171123 1

Preterm birth is a leading cause of global neonate mortality. Hospitalization costs associated with preterm deliveries present a huge economic burden. Existing physical/biochemical markers for predicting preterm birth risk are mostly suited for application at mid/late pregnancy stages, thereby leaving very short time (between diagnosis and delivery) for adopting appropriate intervention strategies. Recent studies indicating correlations between pre/full-term delivery and the composition of vagin ...[more]

PMID: 29170495

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Project description:Despite 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.To 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.This 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.A 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.In 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.

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.

Project description:Objective To develop a pre-pregnancy or first-trimester risk score to identify women at high risk of preterm birth. Study design In this retrospective cohort analysis, the sample was drawn from California singleton livebirths from 2007 to 2012 with linked birth certificate and hospital discharge records. The dataset was divided into a training (2/3 of sample) and a testing (1/3 of sample) set for discovery and validation. Predictive models for preterm birth using pre-pregnancy or first-trimester maternal factors were developed using backward stepwise logistic regression on a training dataset. A risk score for preterm birth was created for each pregnancy using beta-coefficients for each maternal factor remaining in the final multivariable model. Risk score utility was replicated in a testing dataset and by race/ethnicity and payer for prenatal care. Results The sample included 2,339,696 pregnancies divided into training and testing datasets. Twenty-three maternal risk factors were identified including several that were associated with a two or more increased odds of preterm birth (preexisting diabetes, preexisting hypertension, sickle cell anemia, and previous preterm birth). Approximately 40% of women with a risk score ? 3.0 in the training and testing samples delivered preterm (40.6% and 40.8%, respectively) compared to 3.1-3.3% of women with a risk score of 0.0 [odds ratio (OR) 13.0, 95% confidence interval (CI) 10.7-15.8, training; OR 12.2, 95% CI 9.4-15.9, testing). Additionally, over 18% of women with a risk score ? 3.0 had an adverse outcome other than preterm birth. Conclusion Maternal factors that are identifiable prior to pregnancy or during the first-trimester can be used create a cumulative risk score to identify women at the lowest and highest risk for preterm birth regardless of race/ethnicity or socioeconomic status. Further, we found that this cumulative risk score could also identify women at risk for other adverse outcomes who did not have a preterm birth. The risk score is not an effective screening test, but does identify women at very high risk of a preterm birth.

Dataset Information

First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk.

Publications

First-trimester vaginal microbiome diversity: A potential indicator of preterm delivery risk.

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