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Comprehensive proteomic investigation of infectious and inflammatory changes in late preterm prelabour rupture of membranes.

ABSTRACT: Preterm prelabour rupture of membranes beyond the 34th week of gestation (late PPROM) is frequently associated with the risk of the microbial invasion of the amniotic fluid (MIAC) and histological chorioamnionitis (HCA). Hence, we employed a Tandem Mass Tag-based approach to uncover amniotic fluid proteome response to the presence of MIAC and HCA in late PPROM. Protein dysregulation was associated with only five cases in the group of 15 women with confirmed MIAC and HCA. Altogether, 138 amniotic fluid proteins were changed in these five cases exclusively. These proteins were particularly associated with excessive neutrophil responses to infection, such as neutrophil degranulation and extracellular trap formation. We believe that the quantification of these proteins in amniotic fluid may assist in revealing women with the highest risk of excessive inflammatory response in late PPROM.

SUBMITTER: Vajrychova M

PROVIDER: S-EPMC7573586 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Comprehensive proteomic investigation of infectious and inflammatory changes in late preterm prelabour rupture of membranes.

Vajrychová Marie M Stráník Jaroslav J Pimková Kristýna K Barman Malin M Kukla Rudolf R Zedníková Petra P Bolehovská Radka R Plíšková Lenka L Hornychová Helena H Andrýs Ctirad C Tambor Vojtěch V Lenčo Juraj J Jacobsson Bo B Kacerovský Marian M

Scientific reports 20201019 1

Preterm prelabour rupture of membranes beyond the 34th week of gestation (late PPROM) is frequently associated with the risk of the microbial invasion of the amniotic fluid (MIAC) and histological chorioamnionitis (HCA). Hence, we employed a Tandem Mass Tag-based approach to uncover amniotic fluid proteome response to the presence of MIAC and HCA in late PPROM. Protein dysregulation was associated with only five cases in the group of 15 women with confirmed MIAC and HCA. Altogether, 138 amniotic ...[more]

PMID: 33077789

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Project description:BACKGROUND:There is no consensus on the role of inflammatory markers in identifying chorioamnionitis in preterm prelabour rupture of membranes (PPROM). We set out to evaluate the accuracy of maternal blood C-reactive protein (CRP), procalcitonin and interleukin 6 (IL6) in diagnosis of histological chorioamnionitis and/or funisitis (HCA/Funisitis) in PPROM. METHODS:We searched MEDLINE, EMBASE and The Cochrane Library from inception to January 2020 for studies where maternal blood CRP, procalcitonin or IL6 was assessed against a reference standard of HCA/Funisitis in PPROM. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess methodological quality. Hierarchical summary receiver operating characteristic (SROC) models were used to construct summary curves. Bivariate models were used to obtain summary estimates for studies with the same cut-off. RESULTS:We included 23 studies reporting HCA/Funisitis in 902 of 1717 women, median prevalence 50% (inter-quartile range 38-57). Of these studies, 20 were prospective cohort design and 3 were retrospective cohort. Eleven studies reported the index test against a reference standard of HCA and/or funisitis, 10 reported HCA alone and 2 reported funisitis alone. Many studies had high risk of bias scores on the QUADAS-2 assessment but low concerns for applicability. Sensitivity and specificity for CRP ? 20?mg/L (5 studies, 252 participants) was 59% (95% CI 48-69) and 83% (95% CI 74-89) respectively. SROC curves are provided for each index test. At selected specificity of 80%, the sensitivities for CRP (all cut-offs, 17 studies, 1404 participants), PCT ( all cut-offs, 6 studies, 231 participants) and IL6 (all cut-offs, 5 studies, 299 participants) were 59%(95% CI 52-68), 56%(95% CI 50-69) and 52% (95% CI 50-86) respectively. CONCLUSIONS:There is insufficient evidence to support use of CRP, procalcitonin or IL6 in maternal blood for diagnosis of HCA/Funisitis in PPROM. This review followed recommended methodology and data analytic methods that made the most of the data regardless of the different cut-offs used. However, the evidence is based on few studies with generally small sample sizes, poor-quality scores and substantial heterogeneity. There is a need for good-quality diagnostic accuracy studies to better assess the role of these biomarkers in PPROM. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration number: CRD42015023899, registered on 8 October 2015.

Project description:BackgroundGlobally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls.MethodsChorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses.ResultsA total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25.ConclusionsIn 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.

Project description:A 30-year-old in a second pregnancy presented with new-onset spontaneous vaginal discharge of clear liquid for two hours at a gestational age of 29 weeks + 6 days; no other symptoms were present. Movement aggravated vaginal fluid leakage. She appeared anxious but otherwise vitally stable. An immediate ultrasound scan revealed reduced liquor volume. Conservative management was followed by the surgical delivery of a live preterm neonate. The neonate was admitted to the Special Care Baby Unit and the mother was monitored post-surgically in the obstetric ward. Several studies have described the etiology, pathogenesis, and various approaches to the management of Preterm Prelabour Rupture of Membranes (PPROM); however, there is no single global guideline for managing this condition. There is a consensus that PPROM is a notable risk factor for preterm labor, and significantly impacts both maternal and neonatal morbidity, as well as neonatal mortality. We compared epidemiology across other countries to the statistics obtained from Nigeria as well as management guidelines. Studies have also described the advantages of conservative management over proactive surgical intervention in improving neonatal outcomes. Moreover, the management of PPROM is affected by healthcare resources in different countries and their national protocol, and the impact is significant in developing countries like Nigeria such as the age of fetal viability and the lack of a national protocol. This paper explores PPROM and an uncommon presentation of spontaneous PPROM in the South-South region of Nigeria with only drainage of liquor. This case exemplifies the management approaches of PPROM in an underserved community and the factors that affect the survival of neonates in these communities. The index patient was initially managed conservatively and subsequently delivered a live preterm neonate surgically with good APGAR (appearance, pulse, grimace, activity, and respiration) scores. We expect this case report to prompt a unifying guideline for managing PPROM cases while encouraging advanced research and financial support of PPROM screening and treatment in low-income countries.

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.

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Comprehensive proteomic investigation of infectious and inflammatory changes in late preterm prelabour rupture of membranes.

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Comprehensive proteomic investigation of infectious and inflammatory changes in late preterm prelabour rupture of membranes.

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