Dataset Information

Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study.

ABSTRACT: Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA.Gestational age-, birth weight-, delivery mode- and sex- matched (1:2) preterm neonates (< 35 weeks' gestation) born to mothers with or without HCA were enrolled from an observational study. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic analysis was performed on urine samples non-invasively collected in the first 24 hours of life. Univariate analysis, partial least square discriminant analysis (PLS-DA) and its associated variable importance in projection (VIP) score were performed. The most affected metabolic pathways were examined by Metabolite Sets Enrichment Analysis (MSEA).Fifteen cases (mean GA 30.2 ± 3.8 weeks, mean BW 1415 ± 471.9 grams) and 30 controls (mean GA 30.2 ± 2.9 weeks, mean BW 1426 ± 569.8 grams) were enrolled. Following univariate analysis, 29 metabolites had a significantly different concentration between cases and controls. The supervised PLS-DA model confirmed a separation between the two groups. Only gluconic acid, an oxidation product of glucose, was higher in cases than in controls. All other VIP metabolites were more abundant in the control group. Glutamate metabolism, mitochondrial electron transport chain, citric acid cycle, galactose metabolism, and fructose and mannose degradation metabolism were the most significantly altered pathways (P < 0.01).For the first time, urinary metabolomics was able to discriminate neonates born to mothers with and without HCA. The identification of specifically altered metabolic pathways may be helpful in understanding metabolic derangement following chorioamnionitis.

SUBMITTER: Fattuoni C

PROVIDER: S-EPMC5718427 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study.

Fattuoni Claudia C Pietrasanta Carlo C Pugni Lorenza L Ronchi Andrea A Palmas Francesco F Barberini Luigi L Dessì Angelica A Pintus Roberta R Fanos Vassilios V Noto Antonio A Mosca Fabio F

PloS one 20171206 12

<h4>Objective</h4>Chorioamnionitis is a leading cause of preterm birth worldwide, with higher incidence at lower gestational ages. An early and reliable diagnosis of histological chorioamnionitis (HCA) in preterm infants may be helpful in guiding postnatal management, especially the administration of prophylactic antibiotics to prevent early-onset sepsis. The main aim of this study was to investigate metabolomic analysis of urines collected in the first 24 hours of life as diagnostic tool of HCA ...[more]

PMID: 29211784

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Project description:ContextNo consensus exists regarding the association between maternal chorioamnionitis and neurodevelopmental outcomes in preterm and very preterm neonates.ObjectivesTo investigate whether maternal chorioamnionitis affects neurodevelopmental outcomes and to identify the factors that may explain these effects.Data sourcesWe used Ovid Medline, EMBASE and Web of Science to conduct a meta-analysis of studies published in English before August 25, 2017, with titles or abstracts that discussed an association between maternal chorioamnionitis and mental/motor development.Study selectionAmong the 603 initially identified studies, we selected those that addressed an association between maternal chorioamnionitis and mental/motor development according to our preselected inclusion criteria as follows: (1) the study compared infants with and without exposure to maternal chorioamnionitis and (2) the neurodevelopmental outcome was followed up using the Bayley Scales of Infant Development 2nd edition.Data synthesisOur meta-analysis included 10 studies. According to a random effect model, infants with maternal chorioamnionitis exposure had poorer mental development (d = -2.25 [95%CI, -4.33, -0.17], p<0.05) than infants without maternal chorioamnionitis, and infants with maternal clinical chorioamnionitis exposure had poorer motor development (d = -2.37 [95%CI, -4.62 to -0.12], p<0.05) than infants without maternal clinical chorioamnionitis exposure. Factors in the meta-analysis that showed differences between the two patient groups included an MDI assessment blinded to medical history, MDI assessment at the correct age, and time of the MDI assessment.ConclusionThis study suggests that maternal chorioamnionitis may affect mental development in preterm and very preterm neonates, and that maternal clinical chorioamnionitis may affect motor development in offspring. Further studies are required to confirm these results and to detect the influence of variables across studies.

Project description:Background: Histological chorioamnionitis (HCA) is an infection/inflammation of fetal membranes and complicates 5.2-28.5% of all live births. Exposure to HCA can have long-term consequences including abnormal neurodevelopment and an increased risk for allergic disorders and asthma later in childhood. HCA may incite epigenetic changes, which have the potential to modulate both the immune and neurological systems as well as increase the risk of related disorders later in life. However, there is limited data on the impact of HCA on epigenetics, in particular DNA methylation, and changes to immune and neurological systems in full-term human neonates. Objective: To determine differential DNA methylation in cord blood mononuclear leukocytes from neonates exposed to HCA. Methods: Cord blood was collected from 10 term neonates (5 with HCA and 5 controls without HCA) and mononuclear leukocytes were isolated. Genome-wide DNA methylation screening was performed on Genomic DNA extracted from mononuclear leukocytes. Results: Mononuclear leukocytes from cord blood of HCA-exposed neonates showed differential DNA methylation of 68 probe sets compared to the control group (44 hypermethylated, 24 hypomethylated) with a p ≤ 0.0001. Several genes involved in immune modulation and nervous system development were found to be differentially methylated. Important canonical pathways as revealed by Ingenuity Pathway Analysis (IPA) were CREB Signaling in Neurons, FcγRIIB Signaling in B Lymphocytes, Cell Cycle: G1/S Checkpoint Regulation, Interleukin-1, 2, 3, 6, 8, 10, 17, and 17A signaling, p53 signaling, dopamine degradation, and serotonin degradation. The diseases and disorders picked up by IPA were nervous system development and function, neurological disease, respiratory disease, immune cell trafficking, inflammatory response, and immunological disease. Conclusions: HCA induces differential DNA methylation in cord blood mononuclear leukocytes. The differentially methylated genes may contribute to inflammatory, immunological and neurodevelopmental disorders in neonates exposed to HCA.

Project description:Importance:Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm. Objective:To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood. Design, Setting, and Participants:Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks' gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months' corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors. Main Outcomes and Measures:Punctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months' CA. Results:Of 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, -2.2; 95% CI, -5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, -3.0; 95% CI, -6.4 to 0.4). Conclusions and Relevance:Histologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months' CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.

Project description:IntroductionTo identify potential biomarkers in the plasma that could predict histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM), using shotgun and targeted proteomic analyses.MethodsThis retrospective cohort study included 78 singleton pregnant women with PPROM (24-34 gestational weeks) who delivered within 96 h of blood sampling. Maternal plasma samples were analyzed by label-free liquid chromatography-tandem mass spectrometry for proteome profiling in a nested case-control study design (HCA cases vs. non-HCA controls [n = 9 each]). Differential expression of 12 candidate proteins was assessed by multiple reaction monitoring-mass spectrometry (MRM-MS) analysis in individual plasma samples from cases and controls matched by gestational age at sampling (n = 40, cohort 1). A validation study was further performed in an independent study group (n = 38, cohort 2) using ELISA and turbidimetric immunoassay for three differentially expressed proteins.ResultsShotgun proteomics analyses yielded 18 proteins that were differentially expressed (P < 0.05) between HCA cases and non-HCA controls. MRM-MS analysis of 12 differentially expressed proteins further revealed that the CRP, C4A, and SAA4 levels were significantly increased in women with HCA. A multi-marker panel comprising plasma SAA4 and C4A showed enhanced potential for differentiating HCA from non-HCA women (area under the curve = 0.899). Additional validation of these findings by ELISA assays revealed that the CRP levels were significantly higher in women with HCA than in those without HCA, whereas the plasma levels of C4A and SAA4 did not significantly differ between the two groups.ConclusionsPlasma C4A, SAA4, and CRP were identified as potential biomarkers for detecting HCA in women with PPROM, based on targeted and shotgun proteomic analyses, showing good accuracy when used as a combined dual-biomarker panel (C4A and SAA4). Nevertheless, ELISA validation of these proteins, except for CRP, may not yield clinically useful markers for predicting HCA.

Dataset Information

Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study.

Publications

Urinary metabolomic analysis to identify preterm neonates exposed to histological chorioamnionitis: A pilot study.

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