Very preterm delivery is associated with microbial signatures in maternal feces and blood and inflammatory activation in the fetus
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE103192 | GEO | 2020/08/31
REPOSITORIES: GEO
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Project description:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. Currently there is no treatment that can prevent or block preterm labor. In order to identify the molecular regulators of preterm spontaneous labor in the human myometrium, we studied the gene expression profiles of samples with Preterm Spontaneous Labour (PSL) and compared them with the gene expression profiles of samples with Preterm No Labor (PNL).
2021-04-29 | GSE134447 | GEO
Project description:Preterm birth, defined as birth <37 weeks of gestation, is a leading cause of infant morbidity and mortality. In the United States, approximately 12% of all births are preterm.1 Despite decades of research, there has been little progress in developing effective interventions to prevent preterm birth. In fact, the rate of preterm birth has increased slightly over the last several decades.2 The ultimate goal of the Genomic and Proteomic Network for Preterm Birth Research (GPN-PBR) is to identify possible biomarkers that could predict the susceptibility to spontaneous preterm birth (SPTB) as well as to shed light on the molecular mechanisms involved in its etiologies. Understanding those mechanisms will help us predict SPTB and may facilitate the introduction of more effective prevention and treatment strategies.
2014-08-28 | PXD001268 | Pride
Project description:Injury occurring during critical periods of development may have long-term effects on inflammatory responses. Periventricular leukomalacia (PVL) is the most common cause of cerebral palsy (CP) in preterm infant. Activated leukocytes are the main source of inflammatory cytokines that give rise to white matter damage and CP in preterm infant. Here, we tested the hypothesis that inflammation profiles as pathogenic mediators for the occurrence of PVL in the neonatal period may persist in preterm children with CP at school age. Five preterm children with PVL-induced CP and gestational age-matched five preterm children with normal neurodevelopment were recruited from follow up clinics. Proinflammatory gene expression in the PBMCs from preterm children were determined by Superarray PCR study.
2010-05-22 | E-GEOD-17390 | biostudies-arrayexpress
Project description:<p>Preterm labor resulting in the delivery of a premature child is a complex problem with an enormous impact on individuals, families and society. An estimated 500,000 children are born prematurely in the U.S. each year, and 5 million worldwide die annually of prematurity and its complications. Prematurity is also the single largest contributor to disability-adjusted life years, a measure of the lifetime impact of a disease. Despite the importance of the problem and its disproportionate occurrence in poor and minority populations, its underlying etiology (or etiologies) remains unknown; the single best predictor for preterm delivery is a previous preterm birth. The largest single cause of prematurity is spontaneous preterm labor, and suspected triggers for this include infection, stress, poor nutrition and genetic factors. Family and twin studies provide strong evidence that genetic factors underlie about 40% of the risk for prematurity. A major challenge in studying genetic factors in prematurity is maternal/uterine factors, fetal/placental factors, or both may influence risk. Thus, any approach to studying preterm birth should account for both infant and maternal risk, environmental covariates and interactions. The Danish National Birth Cohort (DNBC) is a well-established, prospective cohort that enrolled women early in pregnancy, prior to any adverse pregnancy outcomes, to minimize bias in data collection and sampling. See details at: <a href="http://www.ssi.dk/English" target="_blank">http://www.ssi.dk/English</a>.</p> <p>The DNBC followed over 100,000 pregnancies beginning in the first trimester and has extensive biological material and epidemiologic data on health outcomes in both mother and child. The current study posted on dbGaP contains data from a genome-wide case/control study using approximately 1,000 preterm mother-child pairs from the DNBC most with spontaneous onset of labor or preterm premature rupture of membranes (PPROM), along with 1,000 control pairs where the child was born at ~40 weeks' gestation. After data cleaning some small changes in case/control status and other variables resulted in minor changes in numbers of cases or controls in certain categories. Environmental variables are being used as covariates in the analysis.</p> <p>To replicate positive findings, we are using additional mother-child pairs from the DNBC and from the general Danish population, as well as 2200 samples coming primarily from an African-American population known to have high rates of preterm labor and delivery. This group includes over 1000 mostly very low birthweight infants, over 500 infant term controls, 326 term mother/baby pairs and 180 preterm mother/baby pairs. The data from these additional cohorts will be available in separate dbGaP postings. The study is expected to yield a better understanding of the biology of parturition, identify common genetic factors that play a role in preterm birth and its complications and suggest environmental modifications that can prolong gestation, with the goal of improving both neonatal and adult outcomes.</p> <p>This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>) funded by the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to prematurity and its complications through large-scale genome-wide association studies of a well-characterized cohort of Danish mothers and babies. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.</p>
| phs000103 | dbGaP
Project description:Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. This study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). MeDIP-seq was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p<1e-04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes.
2022-03-09 | GSE194227 | GEO
Project description:Spontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet its prevention and early risk stratification are limited. Previous investigations have suggested that vaginal microbes and metabolites may be implicated in sPTB. Here we performed untargeted metabolomics on 232 second-trimester vaginal samples, 80 from pregnancies ending preterm. We find multiple associations between vaginal metabolites and subsequent preterm birth, and propose that several of these metabolites, including diethanolamine and ethyl glucoside, are exogenous. We observe associations between the metabolome and microbiome profiles previously obtained using 16S ribosomal RNA amplicon sequencing, including correlations between bacteria considered suboptimal, such as Gardnerella vaginalis, and metabolites enriched in term pregnancies, such as tyramine. We investigate these associations using metabolic models. We use machine learning models to predict sPTB risk from metabolite levels, weeks to months before birth, with good accuracy (area under receiver operating characteristic curve of 0.78). These models, which we validate using two external cohorts, are more accurate than microbiome-based and maternal covariates-based models (area under receiver operating characteristic curve of 0.55-0.59). Our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.
2022-11-21 | MTBLS702 | MetaboLights
Project description:We compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with preterm prelabor rupture of membranes (PPROM) deliveries to further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events. Chorioamnion, separated into amnion and chorion, was collected from gestationally age-matched cases and controls within 15 minutes of birth, and analyzed using RNA sequencing. In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.
2024-03-13 | GSE243831 | GEO
Project description:Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and is characterized by impaired alveolar and vascular development. The aim of the study was to identify early BPD-relevant pathways by applying whole genome transcriptional profiling combined with protein measurements from umbilical arterial blood samples of preterm infants with and without BPD. Only newborn infants <32 weeks gestational age (GA) were prospectively included in this study. Blood was obtained from an indwelling umbilical artery catheter at birth and after 72 hours after birth and subjected to gene expression analysis using the Codelink Human I 10k Bioarray and the the Codelink Human Whole Genome Bioarray. The study reveals a monocyte-centered immune response at birth characterizing preterm infants later developing BPD. The findings provide potential markers for early risk stratification in the preterm infant with respect to the development of chronic pulmonary disease and may subsequently enable the development of new treatment strategies in this high risk patient cohort.
| EGAS00001002586 | EGA
Project description:<p>The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Meta-taxonomics data associated with this study are available in the European Nucleotide Archive (ENA): accession number <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB11895' rel='noopener noreferrer' target='_blank'>PRJEB11895</a>, <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB12577' rel='noopener noreferrer' target='_blank'>PRJEB12577</a> and <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB41427' rel='noopener noreferrer' target='_blank'>PRJEB41427</a>.</p>
2021-09-23 | MTBLS717 | MetaboLights
Project description:Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combined multi-parameter flow cytometry, single-cell RNA sequencing (scRNAseq) and targeted plasma analysis to prospectively and longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identified a dynamically changing peripheral blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and monocyte HLA-DR expression, which characterized sepsis even when the common clinical marker of inflammation, C-reactive protein (CRP) was not elevated. Furthermore, scRNAseq showed upregulation of amphiregulin in different leukocyte populations during sepsis, which we validated as a plasma analyte that correlated with clinical signs of disease, even when CRP was normal. This study provides new insights into immune pathways associated with early-life sepsis and identifies potential immune analytes as diagnostic adjuncts for sepsis to guide targeted antibiotic prescribing.
2023-11-23 | GSE236099 | GEO