Metabolomic Profiling of Second-Trimester Amniotic Fluid for Predicting Preterm Delivery: Insights from NMR Analysis.
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SUBMITTER: Kolvatzis C
PROVIDER: S-EPMC10672859 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Metabolomic Profiling of Second-Trimester Amniotic Fluid for Predicting Preterm Delivery: Insights from NMR Analysis.
Kolvatzis Charalampos C Christodoulou Paris P Kalogiannidis Ioannis I Tsiantas Konstantinos K Tsakiridis Ioannis I Kyrkou Charikleia C Cheilari Antigoni A Thomaidis Nikolaos S NS Zoumpoulakis Panagiotis P Athanasiadis Apostolos A Michaelidou Alexandra-Maria AM
Metabolites 20231112 11
Preterm delivery (PTD) is a notable pregnancy complication, affecting one out of every ten births. This study set out to investigate whether analyzing the metabolic composition of amniotic fluid (AF) collected from pregnant women during the second trimester of pregnancy could offer valuable insights into prematurity. The research employed <sup>1</sup>H-NMR metabolomics to examine AF samples obtained from 17 women who gave birth prematurely (between 29<sup>+0</sup> and 36<sup>+5</sup> weeks of ge ...[more]
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Project description:In this article second trimester amniotic fluid biomarkers are measured for correlation with preterm delivery. One additional milliliter of amniotic fluid is collected during amniocentesis for dosages of IL-6, MMP-9, CRP and glucose levels, along with maternal serum CRP and glucose. MMP-9 and Il-6 levels were measured with the corresponding Human Quantikine(R) ELISA Kit (R&D systems) according to the instructions provided by the manufacturer. Cut-off values for AF MMP-9 and IL-6 were fixed by the kit sensitivity thresholds. Data includes ROC curves for glucose (Fig. 1), IL-6 (Fig. 2) and MMP-9 (Fig. 3), aiming to search for sensitivity and specificity in the prediction of premature delivery. Statistical analyses are performed with SPSS v20.0 software. Statistical significance is determined using the Mann-Whitney and one way ANOVA test. The association with preterm delivery is performed using a two proportions test. Correlations are measured using the Pearson׳'s coefficient. A p value<0.05 is considered statistically significant. The data is presented in the figures provided. Data relied on a previous publication "Prediction of preterm delivery by second trimester inflammatory biomarkers in the amniotic fluid" (A. Kesrouani, E. Chalhoub, E. El Rassy, M. Germanos, A. Khazzaka, J. Rizkallah, E. Attieh, N. Aouad, 2016) [1].
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Project description:IntroductionThe global sequence of the pathogenesis of preterm labor remains unclear. This study aimed to compare amniotic fluid concentrations of extracellular matrix-related proteins (procollagen, osteopontin and IL-33), and of cytokines (IL-19, IL-6, IL-20, TNFα, TGFβ, and IL-1β) in asymptomatic women with and without subsequent spontaneous preterm delivery.Material and methodsWe used amniotic fluid samples of singleton pregnancy, collected by amniocentesis between 16 and 20 weeks' gestation, without stigmata of infection (i.e., all amniotic fluid samples were tested with broad-range 16 S rDNA PCR to distinguish samples with evidence of past bacterial infection from sterile ones), during a randomized, double-blind, placebo-controlled trial to perform a nested case-control laboratory study. Cases were women with a spontaneous delivery before 37 weeks of gestation (preterm group). Controls were women who gave birth at or after 39 weeks (full term group). Amniotic fluid concentrations of the extracellular matrix-related proteins and cytokines measured by immunoassays were compared for two study groups.Clinicaltrialsgov: NCT00718705.ResultsBetween July 2008 and July 2011, in 12 maternal-fetal medicine centers in France, 166 women with available PCR-negative amniotic fluid samples were retained for the analysis. Concentrations of procollagen, osteopontin, IL-19, IL-6, IL-20, IL-33, TNFα, TGFβ, and IL-1β were compared between the 37 who gave birth preterm and the 129 women with full-term delivery. Amniotic fluid levels of procollagen, osteopontin, IL-19, IL-33, and TNFα were significantly higher in the preterm than the full-term group. IL-6, IL-20, TGFβ, and IL-1β levels did not differ between the groups.ConclusionsIn amniotic fluid 16 S rDNA PCR negative samples obtained during second-trimester amniocentesis, extracellular matrix-related protein concentrations (procollagen, osteopontin and IL-33), together with IL-19 and TNFα, were observed higher at this time in cases of later spontaneous preterm birth.
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Project description:BACKGROUND:Amniotic fluid is clinically accessible via amniocentesis and its protein composition may correspond to birth timing. Early changes in the amniotic fluid proteome could therefore be associated with the subsequent development of spontaneous preterm delivery. OBJECTIVE:The main objective of this study was to perform unbiased proteomics analysis of the association between mid-trimester amniotic fluid proteome and spontaneous preterm delivery and gestational duration, respectively. A secondary objective was to validate and replicate the findings by enzyme-linked immunosorbent assay using a second independent cohort. METHODS:Women undergoing a mid-trimester genetic amniocentesis at Sahlgrenska University Hospital/Östra between September 2008 and September 2011 were enrolled in this study, designed in three analytical stages; 1) an unbiased proteomic discovery phase using LC-MS analysis of 22 women with subsequent spontaneous preterm delivery (cases) and 37 women who delivered at term (controls), 2) a validation phase of proteins of interest identified in stage 1, and 3) a replication phase of the proteins that passed validation using a second independent cohort consisting of 20 cases and 40 matched controls. RESULTS:Nine proteins were nominally significantly associated with both spontaneous preterm delivery and gestational duration, after adjustment for gestational age at sampling, but none of the proteins were significant after correction for multiple testing. Several of these proteins have previously been described as being associated with spontaneous PTD etiology and six of them were thus validated using enzyme linked immunosorbent assay. Two of the proteins passed validation; Neutrophil gelatinase-associated lipocalin and plasminogen activator inhibitor 1, but the results could not be replicated in a second cohort. CONCLUSIONS:Neutrophil gelatinase-associated lipocalin and Plasminogen activator inhibitor 1 are potential biomarkers of spontaneous preterm delivery and gestational duration but the findings could not be replicated. The negative findings are supported by the fact that none of the nine proteins from the exploratory phase were significant after correction for multiple testing.
| S-EPMC7205297 | biostudies-literature
Project description:ObjectiveThe aim of this study was to identify early proteomic biomarkers of spontaneous preterm delivery (PTD) in mid-trimester amniotic fluid from asymptomatic women.MethodsThis is a case-cohort study. Amniotic fluid from mid-trimester genetic amniocentesis (14-19 weeks of gestation) was collected from 2008 to 2011. The analysis was conducted in 24 healthy women with subsequent spontaneous PTD (cases) and 40 randomly selected healthy women delivering at term (controls). An exploratory phase with proteomics analysis of pooled samples was followed by a verification phase with ELISA of individual case and control samples.ResultsThe median (interquartile range (IQR: 25th; 75th percentiles) gestational age at delivery was 35+5 (33+6-36+6) weeks in women with spontaneous PTD and 40+0 (39+1-40+5) weeks in women who delivered at term. In the exploratory phase, the most pronounced differences were found in C-reactive protein (CRP) levels, that were approximately two-fold higher in the pooled case samples than in the pooled control samples. However, we could not verify these differences with ELISA. The median (25th; 75th IQR) CRP level was 95.2 ng/mL (64.3; 163.5) in women with spontaneous PTD and 86.0 ng/mL (51.2; 145.8) in women delivering at term (p = 0.37; t-test).ConclusionsProteomic analysis with mass spectrometry of mid-trimester amniotic fluid suggests CRP as a potential marker of spontaneous preterm delivery, but this prognostic potential was not verified with ELISA.
| S-EPMC4876998 | biostudies-literature
Project description:Preterm birth affects approximately 5% to 7% of live births worldwide and is the leading cause of neonatal morbidity and mortality. Amniotic fluid supernatant (AFS) contains abundant cell-free nucleic acids (cfNAs) that can provide genetic information associated with pregnancy complications. In the current study, cfNAs of AFS in the early second-trimester before the onset of symptoms of preterm birth were analyzed, and we compared gene expression levels between spontaneous preterm birth (n = 5) and term birth (n = 5) groups using sequencing analysis. Differential expression analyses detected 24 genes with increased and 6 genes with decreased expression in the preterm birth group compared to term birth. Upregulated expressions of RDH14, ZNF572, VOPP1, SERPINA12, and TCF15 were validated in an extended AFS sample by quantitative PCR (preterm birth group, n = 21; term birth group, n = 40). Five candidate genes displayed a significant increase in mRNA expression in immortalized trophoblast HTR-8/SVneo cell with H2O2 treatment. Moreover, the expression of five candidate genes was increased to more than twofold by pretreatment with lipopolysaccharide in HTR-8/SVneo cells. Changes in gene expression between preterm birth and term birth is strongly correlated with oxidative stress and infection during pregnancy. Specific expression patterns of genes could be used as potential markers for the early identification of women at risk of having a spontaneous preterm birth.
| S-EPMC8971495 | biostudies-literature
Project description:ObjectiveBronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring.Study designWe conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools.ResultsOrthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71).ConclusionsThis study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD.
| S-EPMC5068788 | biostudies-literature
Project description:BackgroundThe early colonization and establishment of the microbiome in newborns is a crucial step in the development of the immune system and host metabolism. However, the exact timing of initial microbial colonization remains a subject of ongoing debate. While numerous studies have attempted to determine the presence or absence of intrauterine bacteria, the majority of them have drawn conclusions based on sequencing data from maternal or infant samples taken at a single time point. In this study, we aimed to investigate the microbial population in amniotic fluid (AF) from the second trimester until the time of delivery using multiple microbiological methods.MethodsAF samples were collected during the second trimester (19-21 gestational weeks) and at the time of delivery. Cohort 1 included 51 women who underwent the term and elective cesarean section, with both their second trimester and delivery AF samples (n = 55, respectively) analyzed. Cohort 2 contained 22 women who experienced infection-related adverse pregnancy outcomes (including preterm birth, histological chorioamnionitis, and stillbirth), with only their second trimester AF samples (n = 24) examined. Additionally, multiple procedural negative controls and technical positive controls were applied to this study to remove potential contamination. Microbial profiles were assessed through cultivation, quantitative real-time polymerase chain reaction, 16S ribosomal RNA gene sequencing, and cytokine analysis.ResultsIn cohort 1, the bacterial load and community structure in the second trimester AF samples were indistinguishable from negative controls. Although marginally higher bacterial loads and different bacterial communities were observed in the delivery AF samples compared to negative controls, these bacterial DNA were not considered biologically functional due to the absence of maternal inflammatory responses. In cohort 2, the bacterial load and community structure of the second trimester AF samples differed significantly from those of negative controls, with Ureaplasma and Lactobacillus identified as the most prevalent genera against negative controls.ConclusionsOur study demonstrates that no microorganisms were detected in the AF of healthy pregnancies from the second trimester to the delivery. The presence of Ureaplasma and Lactobacillus in the second trimester AF may be associated with infection-related adverse pregnancy outcomes. Video Abstract.
| S-EPMC11755948 | biostudies-literature
Project description:BackgroundThis study tested if second trimester amniotic fluid cytokine levels, Ureaplasma sp. colonisation and sexual activity predict preterm birth and explain the differential preterm birth rates in Chinese compared to Australian women.MethodsAmniotic fluid was collected by amniocentesis (Chinese 480, Australian 492). Cytokines were measured by multiplex assay and Ureaplasma sp. DNA was detected by PCR analysis. Lifestyle factors, including history of smoking and sexual activity during pregnancy, were obtained through completion of questionnaires upon recruitment to the study.ResultsInflammatory cytokine concentrations were poorly predictive of preterm birth. Ureaplasma sp. was detected in two of the Chinese pregnancies and none from Australia. Sexual activity was less frequent in Chinese, and was not associated with preterm birth or amniotic fluid findings in either population.DiscussionSecond trimester amniocentesis for measurement of inflammatory markers and Ureaplasma sp. DNA was not indicative of risk of preterm birth, at least in these populations. The lower rate of preterm birth in China was not explained by differences in amniotic fluid inflammatory markers, Ureaplasma sp. colonisation, or sexual activity.
| S-EPMC4261245 | biostudies-literature
Project description:ObjectiveAmniotic fluid cytokines have been implicated in the mechanisms of preterm labor and birth. Cytokines can be packaged within or on the surface of extracellular vesicles. The main aim of this study was to test whether the protein abundance internal to and on the surface of extracellular vesicles changes in the presence of sterile intra-amniotic inflammation and proven intra-amniotic infection in women with preterm labor as compared to the women with preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection.Study designWomen who had an episode of preterm labor and underwent an amniocentesis for the diagnosis of intra-amniotic infection or intra-amniotic inflammation were classified into three groups: 1) preterm labor without either intra-amniotic inflammation or proven intra-amniotic infection, 2) preterm labor with sterile intra-amniotic inflammation, and 3) preterm labor with intra-amniotic infection. The concentrations of 38 proteins were determined on the extracellular vesicle surface, within the vesicles, and in the soluble fraction of amniotic fluid.Results1) Intra-amniotic inflammation, regardless of detected microbes, was associated with an increased abundance of amniotic fluid cytokines on the extracellular vesicle surface, within vesicles, and in the soluble fraction. These changes were most prominent in women with proven intra-amniotic infection. 2) Cytokine changes on the surface of extracellular vesicles were correlated with those determined in the soluble fraction; yet the magnitude of the increase was significantly different between these compartments. 3) The performance of prediction models of early preterm delivery based on measurements on the extracellular vesicle surface was equivalent to those based on the soluble fraction.ConclusionsDifferential packaging of amniotic fluid cytokines in extracellular vesicles during preterm labor with sterile intra-amniotic inflammation or proven intra-amniotic infection is reported herein for the first time. The current study provides insights into the biology of the intra-amniotic fluid ad may aid in the development of biomarkers for obstetrical disease.
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Project description:Maternal diabetes and obesity induce marked abnormalities in glucose homeostasis and insulin secretion in the fetus, and are linked to obesity, diabetes, and metabolic disease in the offspring, with specific metabolic characterization based on offspring sex. Gestational diabetes (GDM) has profound effects on the intrauterine milieu, which may reflect and/or modulate the function of the maternal⁻fetal unit. In order to characterize metabolic factors that affect offspring development, we profiled the metabolome of second trimester amniotic fluid (AF) from women who were subsequently diagnosed with gestational diabetes (GDM) using a targeted metabolomics approach, profiling 459 known biochemicals through gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) assays. Using a nested case-control study design, we identified 69 total biochemicals altered by GDM exposure, while sex-specific analysis identified 44 and 58 metabolites in male and female offspring, respectively. The most significant changes were in glucose, amino acid, glutathione, fatty acid, sphingolipid, and bile acid metabolism with specific changes identified based on the offspring sex. Targeted isotope dilution LC/MS confirmatory assays measured significant changes in docosahexaenoic acid and arachidonic acid. We conclude that the sex-specific alterations in GDM maternal⁻fetal metabolism may begin to explain the sex-specific metabolic outcomes seen in offspring exposed to GDM in utero.
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