IMPACT OF RESPIRATORY VIRUS INFECTIONS AND BACTERIAL MICROBIOME SHIFTS ON LYMPHOCYTE AND RESPIRATORY FUNCTION IN INFANTS BORN PREMATURELY OR FULL TERM
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PROVIDER: PRJNA381267 | ENA |
REPOSITORIES: ENA
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Project description:This study aims to compare the cerebellar biochemical profiles in preterm (PT) infants evaluated at term equivalent age (TEA) and healthy full-term newborns using proton magnetic resonance spectroscopy (1H-MRS). We explore the associations between altered cerebellar metabolite profiles and brain injury topography, severity of injury, and prematurity-related clinical complications. We prospectively collected high quality 1H-MRS in 59 premature infants born ≤32 weeks and 61 healthy full term controls. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentration for N-acetyl-aspartate (NAA), choline (Cho) and creatine (Cr). PT infants had significantly lower cerebellar NAA (p < 0.025) and higher Cho (p < 0.001) at TEA when compared to healthy controls. Creatine was not different between the two groups. The presence of cerebellar injury was consistently associated with reduced concentrations for NAA, Cho, and Cr. Postnatal infection was negatively associated with NAA and Cr (p < 005), while cerebral cortical brain injury severity was inversely associated with both Cho and Cr (p < 0.01). We report for the first time that premature birth is associated with altered cerebellar metabolite profiles when compared to term born controls. Infection, cerebellar injury and supratentorial injury are important risk factors for impaired preterm cerebellar biochemistry.
| S-EPMC5557848 | biostudies-other
Project description:ContextPrematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce.ObjectiveTo compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants' amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months.ParticipantsEighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation.OutcomesAmygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months.ResultsAmygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm(3), p < 0.001), and overall right amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm(3), p < 0.001). White matter volumes were significantly smaller (p < 0.001) and CSF volumes significantly larger (p < 0.001) in preterm than in term born infants, while cortical and subcortical gray matter volumes were not significantly different between groups. Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm(3), p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode.ConclusionOur results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development might be linked to alterations in white matter connectivity reported in premature infants. Moreover, our data suggests that such alterations might affect infants' fear-processing capabilities.
| S-EPMC4870280 | biostudies-literature
Project description:Premature birth is associated with high rates of motor and cognitive disability. Investigations have described resting-state functional magnetic resonance imaging (rs-fMRI) correlates of prematurity in older children, but comparable data in the neonatal period remain scarce. We studied 25 term-born control infants within the first week of life and 25 very preterm infants (born at gestational ages ranging from 23 to 29 weeks) without evident structural injury at term equivalent postmenstrual age. Conventional resting-state network (RSN) mapping revealed only modest differences between the term and prematurely born infants, in accordance with previous work. However, clear group differences were observed in quantitative analyses based on correlation and covariance matrices representing the functional MRI time series extracted from 31 regions of interest in 7 RSNs. In addition, the maximum likelihood dimensionality estimates of the group-averaged covariance matrices in the term and preterm infants were 5 and 3, respectively, indicating that prematurity leads to a reduction in the complexity of rs-fMRI covariance structure. These findings highlight the importance of quantitative analyses of rs-fMRI data and suggest a more sensitive method for delineating the effects of preterm birth in infants without evident structural injury.
| S-EPMC4677980 | biostudies-literature
Project description:The rate of cesarean delivery (CD) in China has risen sharply and the high rate was reported to be associated with increased risk of disease in the offspring. However, there is little research on the molecular mechanism of critical pathways and gene signatures involved in the neonatal immunity of cesarean-born infants. This study was undertaken to identify unique gene signatures which was involved in the neonatal immunity of cesarean-born infants through large-scale RNA-sequencing. Genes differentially expressed in cesarean-born infants were identified and further validated through quantitative real-time PCR (RT-qPCR). Moreover, we employed weighted gene co-expression network analysis (WGCNA) to identify highly connected genes that were correlated with neonatal inflammation. In total, 73 differentially expressed genes (DEGs) were identified between cesarean-born infants and normal vagina childbirth. The results obtained by secondary validation indicated that GATM, MIF, IFI27, IL1B, CA1, and EPHB1 were significantly upregulated in phenotype CD, while CYP2A6 and DLK1 were significantly down regulated. Further, functional and pathway enrichment analysis reveals perturbation of several DEGs involved in signaling pathways pertaining to immunoregulation, inflammation, apoptosis, and nervous development. Additionally, HLA-DOB popped out as a core gene in the process of inflammation, which might indicate the risk of cesarean-born infants for inflammatory disease. Notably, our study for the first time has documented gene signatures PIK3CA, PTPRC, SOS1, IL6ST, and MALT1, which were found to be involved in neonatal inflammation. Taken together, the full expression repertoire including the differentially expressed gene sets and core differentially co-expressed genes should provide an excellent resource for identifying potential biomarkers of cesarean-born infants with inflammation, and formulating new hypotheses for physiological functions and the discovery of novel therapeutic targets for inflammatory disease.
2019-01-23 | GSE125421 | GEO
Project description:BACKGROUND:Clostridium perfringens forms part of the human gut microbiota and has been associated with life-threatening necrotising enterocolitis (NEC) in premature infants. Whether specific toxigenic strains are responsible is unknown, as is the extent of diversity of strains in healthy premature babies. We investigated the C. perfringens carrier status of premature infants in the neonatal intensive care unit, factors influence this status, and the toxic potential of the strains. METHODS:C. perfringens was isolated by culture from faecal samples from 333 infants and their toxin gene profiles analysed by PCR. A survival analysis was used to identify factors affecting probability of carriage. Competitive growth experiments were used to explore the results of the survival analysis. RESULTS:29.4% of infants were colonized with C. perfringens before they left hospital. Three factors were inversely associated with probability of carriage: increased duration of maternal milk feeds, CPAP oxygen treatment and antibiotic treatment. C. perfringens grew poorly in breast milk and was significantly outperformed by Bifidobacterium infantis, whether grown together or separately. Toxin gene screening revealed that infants carried isolates positive for collagenase, perfringolysin O, beta 2, beta, becA/B, netB and enterotoxin toxin genes, yet none were observed to be associated with the development of NEC. CONCLUSIONS:Approximately a third of preterm infants are colonised 3 weeks after birth with toxin gene-carrying C. perfringens. We speculate that increased maternal breast milk, oxygen and antibiotic treatment creates an environment in the gut hostile to growth of C. perfringens. Whilst potentially toxigenic C. perfringens isolates were frequent, no toxin type was associated with NEC. TRIAL REGISTRATION:clinicaltrials.gov NCT01102738, registered 13th April 2010.
| S-EPMC7027286 | biostudies-literature
Project description:The cerebral white matter is vulnerable to injury in very preterm infants (born prior to 30 weeks gestation), resulting in a spectrum of lesions. These range from severe forms, including cystic periventricular leukomalacia and periventricular hemorrhagic infarction, to minor focal punctate lesions. Moderate to severe white matter injury in preterm infants has been shown to predict later neurodevelopmental disability, although outcomes can vary widely in infants with qualitatively comparable lesions. Resting state functional connectivity magnetic resonance imaging has been increasingly utilized in neurodevelopmental investigations and may provide complementary information regarding the impact of white matter injury on the developing brain. We performed resting state functional connectivity magnetic resonance imaging at term equivalent postmenstrual age in fourteen preterm infants with moderate to severe white matter injury secondary to periventricular hemorrhagic infarction. In these subjects, resting state networks were identifiable throughout the brain. Patterns of aberrant functional connectivity were observed and depended upon injury severity. Comparisons were performed against data obtained from prematurely-born infants with mild white matter injury and healthy, term-born infants and demonstrated group differences. These results reveal structural-functional correlates of preterm white matter injury and carry implications for future investigations of neurodevelopmental disability.
| S-EPMC3706620 | biostudies-literature
Project description:<p><b>Public health importance</b>: Babies born preterm, approximately 1 out of every 9 live births in the United States, have significant respiratory morbidity over the first two years of life, exacerbated by respiratory viral infections. Many (<50%) return to pediatricians, emergency rooms and pulmonologists with symptoms of respiratory dysfunction (SRD): intermittent or chronic wheezing, poor growth and an excess of upper and lower respiratory tract infections (LRTI). SRD correlate inversely with gestational age and weight at birth and is more common in those with chronic lung disease of prematurity, yet its incidence and severity varies widely among both the prematurely born and those born at term. There is evidence from clinical studies and animal models that risks of LRTI and recurrent wheezing is influenced by gut and respiratory flora and by T cell responses to infection. Information gained from this study will be used to identify characteristics, risk factors and potential mechanisms for early and persistent lung disease in children born at term and born preterm.</p> <p>This Clinical Research Study will investigate the relationships between sequential respiratory viral infections, patterns of intestinal and respiratory bacterial colonization, and adaptive cellular immune phenotypes which are associated with increased susceptibility to respiratory infections and long term respiratory morbidity in preterm and full term infants. We hypothesize that the timing and acquisition of specific viral infections and bacterial species are directly related to respiratory morbidity in the first year of life as defined by SRD and by measures of pulmonary function. We hypothesize that cellular and molecular immuno-maturity are altered due to factors presented by premature birth in such a way as to promote chronic inflammatory and cytotoxic damage to the lung, with subsequent enhanced, damaging responses to infectious agents and environmental irritants. Our preliminary studies demonstrate both feasibility and expertise in mutiparameter immunophenotyping of small volume peripheral blood samples obtained from premature infants including gene expression arrays of flow cytometry sorted cells. We will use new technologies for known viral identification, as well as high-throughput metagenome sequencing of RNA and DNA virus like particles (VLP) to be used for viral discovery in infant respiratory sample and use of high-throughput pyrosequencing (454T) of bacterial 16S rRNA to determine shifts in bacterial community structure, occurring in pre-term (PT) as compared to full term (FT) infants, over the first year of life. Finally, we present statistical approaches to stratify disease risk predictors using multivariate logistic regression modeling approaches. We propose to evaluate T cell phenotypic and functional profiles relative to viral and predominant bacterial exposures according to highly complementary, but independent, Specific Objectives.</p> <p><b>Objective 1</b>: To determine if viral respiratory infections and patterns of respiratory and gut bacterial community structure (microbiome) in prematurely born babies predict the rate and degree of immunologic maturation, and pulmonary dysfunction, measured from birth to 36 weeks corrected gestational age (CGA).</p> <p><b>Objective 2</b>: To determine the relationship between respiratory viral infections and disease severity up to one year CGA, and the lymphocyte (Lc) phenotypes documented at term gestation (birth for term infants and 36 wks/NICU discharge in preterm infants) and at one year CGA. Three secondary outcomes of this objective will be to a) relate the quantity, type and severity of viral infections with pulmonary function at one and three years of life, b) relate the viral community structure to severity of viral infections and c) to seek evidence of modulation of viral susceptibility by bacterial respiratory and gut community structure (microbiome). The relationship of colonization with known and non-identified bacterial species in both the respiratory tract and the gut will be evaluated. </p>
| phs001347 | dbGaP
Project description:ImportanceSurvivors of preterm birth often present with medical morbidities; however, variation in their long-term educational performance has not been well described.ObjectiveTo estimate the association between gestational age and 4 outcomes in school-aged children: readiness to enter kindergarten, scores on standardized tests in elementary and middle school, gifted status, and low performance.Design, setting, and participantsIn a retrospective cohort study, children born in Florida between 1992 and 2002 at 23 to 41 weeks' gestation who entered Florida's public schools between 1995 and 2012 were assessed for kindergarten readiness and tested in mathematics and reading in grades 3 through 8. Data analysis was performed from January 12, 2016, to March 1, 2017.ExposuresGestational age at birth.Main outcomes and measuresKindergarten readiness, scores on the Florida Comprehensive Achievement Test (FCAT), classified as gifted, and classified as low performance.ResultsA total of 1?527?113 singleton infants with gestational ages of 23 to 41 weeks born between 1992 and 2002 were matched to Florida public school records. Of these, 1?301?497 children were included in the analysis; 641?479 (49.3%) were girls. A total of 301 (65.0%) Florida children born at 23 to 24 weeks' gestation were designated as ready to start kindergarten. When the FCAT test scores were adjusted for potentially confounding maternal and infant variables, children born at 23 to 24 weeks' gestation performed 0.66 SD (95% CI, -0.73 to -0.59) lower compared with those born at full term. A total of 123?554 (9.5%) of all Florida-born public school students were considered gifted, including 17 (1.8%) of those born at 23 to 24 weeks' gestation. In comparison, 75?458 (5.8%) of all Florida-born public school students were low performing; 310 (33.5%) of these children had been born at 23 to 24 weeks' gestation. Kindergarten readiness, FCAT scores, and gifted status were positively related to gestational age, whereas low performance was inversely related to gestational age.Conclusions and relevanceAlthough gestational age has long been associated with poor educational performance, a sufficient proportion of children born near the limits of viability performed within expected school norms, warranting further investigation into how and why certain children are able to overcome the educational burdens that may follow preterm birth.
| S-EPMC5710633 | biostudies-literature
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 470 cord blood samples from infants born to women in the Southampton Women's Survery (SWS) cohort, to examine the association between DNA methylation in the infant and aspects of health and disease in early and life and childhood.
2021-08-18 | GSE154915 | GEO
Project description:Genome-wide DNA methylation profiling of umbilical cord blood buffy coat DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 557 cord blood samples born to obese women in the UPBEAT trial, with and without gestational diabetes mellitus (GDM), to determine the association between maternal GDM and hyperglycaemia during pregnancy on the methylation in the infant.
2020-11-05 | GSE141065 | GEO