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Women with preterm birth have a distinct cervicovaginal metabolome.

ABSTRACT: 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.

SUBMITTER: Ghartey J

PROVIDER: S-EPMC4877183 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Women with preterm birth have a distinct cervicovaginal metabolome.

Ghartey Jeny J Bastek Jamie A JA Brown Amy G AG Anglim Laura L Elovitz Michal A MA

American journal of obstetrics and gynecology 20150328 6

<h4>Objective</h4>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.<h4>Study design</h4>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 ...[more]

PMID: 25827503

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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.

Project description:ObjectivesPerturbation of the choriodecidual space before the onset of spontaneous preterm birth (sPTB) could lead to a concomitant rise in both cervicovaginal fluid (CVF) cytokine and fetal fibronectin (FFN), and assessing the concentrations of both markers could improve the prediction of sPTB (delivery before 37 completed weeks of gestation). Therefore, we prospectively determined mid-trimester changes in CVF cytokine and FFN concentrations, and their predictive capacity for sPTB in asymptomatic pregnant women.Study designCVF collected at 20+0-22+6 weeks (n = 47: Preterm-delivered = 22, Term-delivered = 25) and 26+0-28+6 weeks (n = 50: Preterm-delivered = 17, Term-delivered = 33) from 63 asymptomatic pregnant women at risk of sPTB were examined. Cytokine and FFN concentrations were determined by multiplexed bead-based immunoassay and 10Q Rapid analysis (Hologic, MA, USA) respectively. The 20+0-22+6/26+0-28+6 weeks ratios of cytokines and FFN concentrations were compared between preterm- and term-delivered women using Receiver Operating Characteristics curves to predict sPTB. Also, bacterial 16S rDNA from 64 samples (20+0-22+6 weeks n = 36, 26+0-28+6 weeks n = 28) was amplified by polymerase chain reaction to determine associations between vaginal microflora, cytokine and FFN concentrations.ResultsChanges in RANTES and IL-1β concentrations between 20+0-22+6 and 26+0-28+6 weeks, expressed as a ratios, were predictive of sPTB, RANTES (AUC = 0.82, CI = 0.62-0.94) more so than IL-1β (AUC = 0.71, CI = 0.53-0.85) and FFN (not predictive). Combining these markers (AUC = 0.83, CI = 0.63-0.95) showed similar predictive capacity as RANTES alone. FFN concentrations at 26+0-28+6 weeks correlated with IL-1β (r = 0.4, P = 0.002) and RANTES (r = 0.3, P = 0.03). In addition, there was increased prevalence of vaginal anaerobes including Bacteroides, Fusobacterium and Mobiluncus between gestational time points in women who experienced sPTB compared to the term women (P = 0.0006).ConclusionsCVF RANTES and IL-1β in mid-trimester of pregnancy correlate with quantitative FFN. The levels of CVF RANTES and IL-1β decline significantly in women who deliver at term unlike women who deliver preterm. This observation suggests that sPTB may be characterised by sustained choriodecidual inflammation and may have clinical value in serial screening for sPTB if confirmed by larger studies.

Dataset Information

Women with preterm birth have a distinct cervicovaginal metabolome.

Publications

Women with preterm birth have a distinct cervicovaginal metabolome.

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