Project description:Maternal plasma samples collected longitudinally from pregnant women were profiled using SomaLogic aptamer-based assays in women with normal pregnancy and those who delivered preterm. DiagnosisGA is the gestational age at diagnosis with any disease indicated by the Group variable, and it is set to NA for normal pregnancies. In the Group variable, sPTD stands for spontaneous preterm delivery, and PPROM for preterm premature rupture of membranes. Additional longitudinal samples of the controls, including the two samples included herein, are also available and described in PMID: 28738067.
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.
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).
Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The studyâ??s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5â?? and 3â??UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. 183 total RNA samples from 8 tissue types collected from 35 women grouped into six categories of pregnancy outcome. One microarray replicate per sample. Other Contributors: Radek Bukowski, Sam Parry and the NICHD Genomic and Proteomic Network for Preterm Birth Research
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>
Project description:Preterm birth is often predisposed by chorioamnionitis (CA) and CA affects the fetal gut and lungs via intra-amniotic (IA) inflammation, thus accentuating the proinflammatory effects of preterm birth. It is not known if IA inflammation also affects other perfusion-sensitive organs (e.g., kidneys) before and after preterm birth. Using preterm pigs as model for preterm infants, we hypothesized that CA induces fetal and neonatal renal dysfunctions that can intially be detected via plasma proteome, partly explaining the frequent renal dysfunction in preterm infants. Fetal pigs (88% gestation) were given an IA dose of lipopolysaccharide (LPS, 1 mg/kg, n=28), delivered preterm by cesarean section three days later, and compared with controls (CON, n=26) at birth and postnatal day five. Plasma proteome and protein markers of inflammatory pathways were evaluated.
Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. The study’s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5’ and 3’UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.
Project description:The objective of this study was to characterise the changes in the exosomal miRNA concentrations circulating in the maternal plasma between mothers delivering term and preterm neonates, across gestation using a longitudinal study design. A retrospective stratified study design was used to characterize the miRNA content in exosomes present in maternal plasma of term (n=20 per time point) and preterm birth (PTB) (n=10 per time point) across gestation (i.e. first, second and third trimester).
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.
Project description:Threatened preterm labour (TPTL) is the most common condition that requires hospitalisation during pregnancy. Most of these symptomatic women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. Peripheral blood leukocytes are exposed to “activating signals” from reproductive tissues and may indicate the impending onset of labour. Objectives: 1) To investigate differential leukocyte gene expression in women with TPTL; and 2) to develop a gene signature to predict preterm birth (PTB) within 48 hours in symptomatic women. Design, Setting and Participants: Women clinically diagnosed with TPTL were recruited. Peripheral blood was obtained at point of admission prior to medical treatments. mRNA was extracted and microarrays (Affymetrix U133 Plus 2.0) were utilised to determine differential gene expressions between women who did (n=48) and did not (n=106) have a preterm delivery within 48 hours of hospital admission. Results: There were 394 significantly differentially expressed genes (FDR<0.05, Limma); 22 out of 30 genes chosen for qRT-PCR validation were differentially expressed (p<0.05). Total 154; 48 delivered within 48 hours of hospital admission; 106 did not deliver within 48 hours