Metabolite Profile of Cervicovaginal Fluids from Early Pregnancy Is Not Predictive of Spontaneous Preterm Birth.
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ABSTRACT:
SUBMITTER: Thomas MM
PROVIDER: S-EPMC4661910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Peripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
2020-02-10 | GSE142974 | GEO
Project description:Twin pregnancies are associated with a three-fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply.To review the burden of preterm birth in multiple pregnancy.To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.To be aware of the use of the Arabin pessary.
| S-EPMC6034359 | biostudies-other
Project description:BackgroundWe conducted a literature review on the studies that investigated the relationship of preterm birth, including spontaneous preterm birth (sPTB), with vitamin D status. Overall, these studies demonstrated that the incidence of sPTB was associated with maternal vitamin D insufficiency in early pregnancy. However, the potential mechanisms and biological pathways are unknown.ObjectivesTo investigate early pregnancy gene expression signatures associated with both vitamin D insufficiency and sPTB. We further constructed a network of these gene signatures and identified the common biological pathways involved.Study designWe conducted peripheral blood transcriptome profiling at 10-18 weeks of gestation in a nested case-control cohort of 24 pregnant women who participated in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). In this cohort, 8 women had spontaneous preterm delivery (21-32 weeks of gestation) and 17 women had vitamin D insufficiency (25-hydroxyvitamin D < 30 ng/mL). We separately identified vitamin D-associated and sPTB gene signatures at 10 to 18 weeks and replicated the overlapping signatures in the mid-pregnancy peripheral blood of an independent cohort with sPTB cases.ResultAt 10-18 weeks of gestation, 146 differentially expressed genes (25 upregulated) were associated with both vitamin D insufficiency and sPTB in the discovery cohort (FDR < 0.05). Of these genes, 43 (25 upregulated) were replicated in the independent cohort of sPTB cases and controls with normal pregnancies (P < 0.05). Functional enrichment and network analyses of the replicated gene signatures suggested several highly connected nodes related to inflammatory and immune responses.ConclusionsOur gene expression study and network analyses suggest that the dysregulation of immune response pathways due to early pregnancy vitamin D insufficiency may contribute to the pathobiology of sPTB.
| S-EPMC6988958 | biostudies-literature
Project description:BackgroundWater total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown.ObjectiveInvestigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels.DesignMethods: This was a secondary analysis of participants (n = 474) in the Motherhood & Microbiome (M&M) study (n = 2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks' gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized.ResultsParticipants' water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p < 0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8 [13.5] vs. 41.8 [11.8], p = 0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39]) per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (β 0.17 [95%CI: -0.15, 0.49]), interaction p = 0.013).ConclusionWe did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted.
| S-EPMC8195861 | biostudies-literature
Project description:ObjectiveHere, we investigated whether cytokines in the cervicovaginal fluid (CVF) can be predictive markers of preterm birth (PTB).MethodsA multi-center prospective cohort study was conducted on 59 singleton pregnant women hospitalized for preterm labor (PTL) and/or preterm premature rupture of membranes (pPROM) between 22 weeks and 36 weeks 6 days of gestation from 2014 to 2015. The levels of 13 inflammatory cytokines (macrophage inflammatory protein [MIP]-1α, MIP-1β, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-8, IL-17α, granulocyte colony stimulating factor [G-CSF], IL-7, IL-4, IL-5, IL-10, and IL-13) were measured using a multiplex bead-based immunoassay and that of fetal fibronectin (fFN) was measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using Student's t-test, Mann-Whitney U test, Pearson's correlation, and receiver operating characteristic (ROC) curve analysis in SPSS version 20.0.ResultsAmong the 13 cytokines assessed, the levels of 3 cytokines (MIP-1α, IL-6, and IL-7) were negatively correlated with gestational age at delivery (P=0.028, P=0.002, and P=0.018, respectively). Sensitivities of MIP-1α, IL-6, and IL-17α were 70%, 80%, and 75%, respectively, and their specificities were 57%, 65%, and 69%, respectively. The sensitivity and specificity of fFN were 33% and 95%, respectively.ConclusionIn symptomatic women diagnosed with PTL and/or pPROM, cytokines from cervicovaginal fluid, especially IL-6 and IL-17α, could be better predictive markers of PTB than fFN.
| S-EPMC7393743 | 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
Project description:IntroductionPreterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles.ObjectivesWe sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB.MethodsA 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.ResultsSix 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.ConclusionHigh 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: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.
| S-EPMC5886036 | biostudies-literature
Project description:Transcriptome analysis of preterm and term placentas
2021-08-10 | GSE120480 | GEO
Project description:ObjectiveTo determine the accuracy with which a cervicovaginal fetal fibronectin test predicts spontaneous preterm birth in women with or without symptoms of preterm labour.DesignSystematic quantitative review of studies of test accuracy.Data sourcesMedline, 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 selectionTwo reviewers independently selected and extracted data on study characteristics, quality, and accuracy.Data extractionAccuracy 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 synthesis64 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).ConclusionCervicovaginal 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