Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.
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ABSTRACT:
SUBMITTER: Flaviani F
PROVIDER: S-EPMC8410012 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Metabolomics has the potential to reveal novel pathways involved in the pathogenesis of preterm birth (PTB). The objective of this study was to investigate whether the cervicovaginal (CV) metabolome was different in asymptomatic women destined to have a PTB compared with term birth.A nested case-control study was performed using CV fluid collected from a larger prospective cohort. The CV fluid was collected between 20-24 weeks (V1) and 24-28 weeks (V2). The metabolome was compared between women with a spontaneous PTB (n = 10) to women who delivered at term (n = 10). Samples were extracted and prepared for analysis using a standard extraction solvent method. Global biochemical profiles were determined using gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. An ANOVA was used to detect differences in biochemical compounds between the groups. A false discovery rate was estimated to account for multiple comparisons.A total of 313 biochemicals were identified in CV fluid. Eighty-two biochemicals were different in the CV fluid at V1 in those destined to have a PTB compared with term birth, whereas 48 were different at V2. Amino acid, carbohydrate, and peptide metabolites were distinct between women with and without PTB.These data suggest that the CV space is metabolically active during pregnancy. Changes in the CV metabolome may be observed weeks, if not months, prior to any clinical symptoms. Understanding the CV metabolome may hold promise for unraveling the pathogenesis of PTB and may provide novel biomarkers to identify women most at risk.
| S-EPMC4877183 | biostudies-literature
Project description:Failure to predict and understand the causes of preterm birth, the leading cause of neonatal morbidity and mortality, have limited effective interventions and therapeutics. From a cohort of 2000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Using innovative Bayesian modeling of cervicovaginal microbiota, seven bacterial taxa were significantly associated with increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of β-defensin-2 lowered the risk of sPTB associated with cervicovaginal microbiota in an ethnicity-dependent manner. Surprisingly, even in Lactobacillus spp. dominated cervicovaginal microbiota, low β-defensin-2 was associated with increased risk of sPTB. These findings hold promise for diagnostics to accurately identify women at risk for sPTB early in pregnancy. Therapeutic strategies could include immune modulators and microbiome-based therapeutics to reduce this significant health burden.
| S-EPMC6428888 | biostudies-literature
Project description:OBJECTIVE:To determine the accuracy with which a cervicovaginal fetal fibronectin test predicts spontaneous preterm birth in women with or without symptoms of preterm labour. DESIGN:Systematic quantitative review of studies of test accuracy. DATA SOURCES:Medline, Embase, PASCAL, Biosis, Cochrane Library, Medion, National Research Register, SCISEARCH, conference papers, manual searching of bibliographies of known primary and review articles, and contact with experts and manufacturer. STUDY SELECTION:Two reviewers independently selected and extracted data on study characteristics, quality, and accuracy. DATA EXTRACTION:Accuracy data were used to form 2x2 contingency tables with spontaneous preterm birth before 34 and 37 weeks' gestation and birth within 7-10 days of testing (for symptomatic pregnant women) as reference standards. Data were pooled to produce summary receiver operating characteristic curves and summary likelihood ratios for positive and negative test results. DATA SYNTHESIS:64 primary articles were identified, consisting of 28 studies in asymptomatic women and 40 in symptomatic women, with a total of 26 876 women. Among asymptomatic women the best summary likelihood ratio for positive results was 4.01 (95% confidence interval 2.93 to 5.49) for predicting birth before 34 weeks' gestation, with corresponding summary likelihood ratio for negative results of 0.78 (0.72 to 0.84). Among symptomatic women the best summary likelihood ratio for positive results was 5.42 (4.36 to 6.74) for predicting birth within 7-10 days of testing, with corresponding ratio for negative results of 0.25 (0.20 to 0.31). CONCLUSION:Cervicovaginal fetal fibronectin test is most accurate in predicting spontaneous preterm birth within 7-10 days of testing among women with symptoms of threatened preterm birth before advanced cervical dilatation.
| S-EPMC117763 | biostudies-literature
Project description:ObjectiveThis study developed and internally validated a predictive model for preterm birth (PTB) to examine the ability of neighbourhood socioeconomic status (SES) to predict PTB.DesignCohort study using individual-level data from two community-based prospective pregnancy cohort studies (All Our Families (AOF) and Alberta Pregnancy Outcomes and Nutrition (APrON)) and neighbourhood SES data from the 2011 Canadian census.SettingCalgary, Alberta, Canada.ParticipantsPregnant women who were <24 weeks of gestation and >15 years old were enrolled in the cohort studies between 2008 and 2012. Overall, 5297 women participated in at least one of these cohorts: 3341 women participated in the AOF study, 2187 women participated in the APrON study and 231 women participated in both studies. Women who participated in both studies were only counted once.Primary and secondary outcome measuresPTB (delivery prior to 37 weeks of gestation).ResultsThe rates of PTB in the least and most deprived neighbourhoods were 7.54% and 10.64%, respectively. Neighbourhood variation in PTB was 0.20, with an intra-class correlation of 5.72%. Neighbourhood SES, combined with individual-level predictors, predicted PTB with an area under the receiver-operating characteristic curve (AUC) of 0.75. The sensitivity was 91.80% at a low-risk threshold, with a high false-positive rate (71.50%), and the sensitivity was 5.70% at a highest risk threshold, with a low false-positive rate (0.90%). An agreement between the predicted and observed PTB demonstrated modest model calibration. Individual-level predictors alone predicted PTB with an AUC of 0.60.ConclusionAlthough neighbourhood SES combined with individual-level predictors improved the overall prediction of PTB compared with individual-level predictors alone, the detection rate was insufficient for application in clinical or public health practice. A prediction model with better predictive ability is required to effectively find women at high risk of preterm delivery.
| S-EPMC6398791 | biostudies-literature
Project description:Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome-wide association studies (GWAS) variants (P < 5 × 10-8 ) and 17 other variants associated with NAFLD were examined in a nested case-control study of NAFLD (1,448 cases/8,444 controls) in this multi-ethnic cohort study. We then built a GRS using 11 independent single-nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated (P < 0.05) in the pooled multi-ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin-like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G-patch domain containing 1), MBOAT7 (membrane bound O-acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)-CHUK (component of inhibitor of nuclear factor kappa B kinase complex)-CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11-SNP weighted GRS was associated with NAFLD risk in the multi-ethnic population (odds ratio [OR] per SD increase = 1.41; 95% confidence interval [CI] = 1.32-1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS-NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46-1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28-1.46) (P heterogeneity = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
| S-EPMC8485887 | biostudies-literature
Project description:CIDR Preterm Birth Boston Cohort
| PRJNA75541 | ENA
Project description:OBJECTIVE: The association between low birth weight and type 2 diabetes is well established. We studied whether preterm birth carries a similar risk. RESEARCH DESIGN AND METHODS: The Helsinki Birth Cohort includes 13,345 men and women born between 1934 and 1944. Of them, 12,813 had adequate data on length of gestation, which we linked with data on special reimbursement for diabetes medication. RESULTS: Of the subjects, 5.1% had received special reimbursement after age 40. In subjects born before 35 weeks of gestation, the odds ratio for diabetes was 1.68 (95% CI 1.06-2.65) compared with that in those born at term. After adjustment for birth weight relative to length of gestation, the odds ratio was 1.59 (1.00-2.52). CONCLUSIONS: Preterm birth before 35 weeks of gestation is associated with an increased risk of type 2 diabetes in adult life. The risk is independent of that associated with slow fetal growth.
| S-EPMC2992201 | biostudies-other
Project description:INTRODUCTION:Bacterial vaginosis (BV) and vaginal microbiota disruption during pregnancy are associated with increased risk of spontaneous preterm birth (SPTB), but clinical trials of BV treatment during pregnancy have shown little or no benefit. An alternative hypothesis is that vaginal bacteria present around conception may lead to SPTB by compromising the protective effects of cervical mucus, colonising the endometrial surface before fetal membrane development, and causing low-level inflammation in the decidua, placenta and fetal membranes. This protocol describes a prospective case-cohort study addressing this hypothesis. METHODS AND ANALYSIS:HIV-seronegative Kenyan women with fertility intent are followed from preconception through pregnancy, delivery and early postpartum. Participants provide monthly vaginal specimens during the preconception period for vaginal microbiota assessment. Estimated date of delivery is determined by last menstrual period and first trimester obstetrical ultrasound. After delivery, a swab is collected from between the fetal membranes. Placenta and umbilical cord samples are collected for histopathology. Broad-range 16S rRNA gene PCR and deep sequencing of preconception vaginal specimens will assess species richness and diversity in women with SPTB versus term delivery. Concentrations of key bacterial species will be compared using quantitative PCR (qPCR). Taxon-directed qPCR will also be used to quantify bacteria from fetal membrane samples and evaluate the association between bacterial concentrations and histopathological evidence of inflammation in the fetal membranes, placenta and umbilical cord. ETHICS AND DISSEMINATION:This study was approved by ethics committees at Kenyatta National Hospital and the University of Washington. Results will be disseminated to clinicians at study sites and partner institutions, presented at conferences and published in peer-reviewed journals. The findings of this study could shift the paradigm for thinking about the mechanisms linking vaginal microbiota and prematurity by focusing attention on the preconception vaginal microbiota as a mediator of SPTB.
| S-EPMC7045118 | biostudies-literature
Project description:INTRODUCTION:Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. OBJECTIVES:We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. METHODS:A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20-22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20-22 g.w., n = 71, and 26-28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24-36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. RESULTS:Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p < 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20-22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20-22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61-0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64-1) in the SYM women, whilst other metabolites were not. CONCLUSION:High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.
| S-EPMC4783437 | biostudies-literature
Project description:Changes in vaginal microbiota that is associated with preterm birth (PTB) leave specific metabolite fingerprints that can be detected in the cervicovaginal fluid (CVF) using metabolomics techniques. In this study, we characterize and validate the CVF metabolite profile of pregnant women presenting with symptoms of threatened preterm labor (PTL) by both 1H-nuclear magnetic resonance spectroscopy (NMR) and enzyme-based spectrophotometry. We also determine their predictive capacity for PTB, singly, and in combination, with current clinical screening tools - cervicovaginal fetal fibronectin (FFN) and ultrasound cervical length (CL). CVF was obtained by high-vaginal swabs from 82 pregnant women with intact fetal membranes presenting between 24 and 36?weeks gestation with symptoms of threatened, but not established, PTL. Dissolved CVF samples were scanned with a 400?MHz NMR spectrometer. Acetate and other metabolites were identified in the NMR spectrum, integrated for peak area, and normalized to the total spectrum integral. To confirm and validate our observations, acetate concentrations (AceConc) were also determined from a randomly-selected subset of the same samples (n?=?57), by spectrophotometric absorption of NADH using an acetic acid assay kit. CVF FFN level, transvaginal ultrasound CL, and vaginal pH were also ascertained. Acetate normalized integral and AceConc were significantly higher in the women who delivered preterm compared to their term counterparts (P?=?0.002 and P?=?0.006, respectively). The 1H-NMR-derived acetate integrals were strongly correlated with the AceConc estimated by spectrophotometry (r?=?0.69; P?<?0.0001). Both methods were equally predictive of PTB <37?weeks (acetate integral: AUC?=?0.75, 95% CI?=?0.60-0.91; AceConc: AUC?=?0.74, 95% CI?=?0.57-0.90, optimal predictive cutoff of >0.53?g/l), and of delivery within 2?weeks of the index assessment (acetate integral: AUC?=?0.77, 95% CI?=?0.58-0.96; AceConc: AUC?=?0.68, 95% CI?=?0.5-0.9). The predictive accuracy of CVF acetate was similar to CL and FFN. The combination of CVF acetate, FFN, and ultrasound CL in a binary logistic regression model improved the prediction of PTB compared to the three markers individually, but CVF acetate offered no predictive improvement over ultrasound CL combined with CVF FFN. Elevated CVF acetate in women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2?weeks of presentation. An assay of acetate in CVF may prove of clinical utility for predicting PTB.
| S-EPMC5056530 | biostudies-literature