Maternal and neonatal outcomes following expectant management of preterm prelabor rupture of membranes before viability.

Purpose: To provide center-based outcome data on obstetric and neonatal complications arising from expectantly managed pregnancies affected by preterm prelabor rupture of membranes (PPROM) before viability.Materials and methods: We collected data on 130 consecutive pregnancies complicated by spontaneous rupture of membranes before 24 week's gestation, occurring over a 7-year period. These were women who delivered >24 h after membrane rupture, and had no signs of chorioamnionitis or advanced labor at admission. Women with amniocentesis-induced PPROM (n = 7) were analyzed separately. The descriptive statistics of obstetrics and neonatal outcomes were reported.Results: The overall neonatal survival to discharge rate was 33.8%. Stratification of patients into early (12 to 19+6 weeks' gestation) and late pre-viable PPROM (20 to 23+6 weeks' gestation) revealed a 3.6-fold increase in survival rate in the latter group (12.2% versus 43.8%, p < .001). Pre-viable PPROM following amniocentesis predicted a 100% survival outcome, however anhydramnios impacted negatively. The most common neonatal morbidities of those admitted to intensive care unit were respiratory distress syndrome (78.7%) and bronchopulmonary dysplasia (84.4%). The most common maternal morbidities affecting pre-viable PPROM were clinical chorioamnionitis (47.7%), histological chorioamnionitis (81.8%), retained products of conception (39.3%) and preterm labor (45.4%).Conclusions: Later gestational ages at PPROM were associated with better survival rates, however neonatal morbidity remained high. Women experiencing pre-viable PPROM following amniocentesis can be reassured, while those with anhydramnios at any time during the latency period should be adequately counseled regarding poorer outcomes.

Maternal and neonatal outcomes following expectant management of preterm prelabour rupture of membranes before viability.

AIM: To assess the contemporary maternal and neonatal outcomes following expectant management of preterm premature rupture of membranes (PPROM) prior to 24 weeks' gestation and to identify prognostic indicators of this morbid presentation. METHODS: We performed a systematic review in the Pubmed and EMBASE databases to identify the primary (perinatal mortality, severe neonatal morbidity and serious maternal morbidity) and secondary (neonatal survival and morbidity) outcomes following expectant management of previable PPROM. RESULTS: Mean latency between PPROM and delivery ranged between 20 and 43 days. Women with PPROM <24 weeks had an overall live birth rate of 63.6% and a survival-to-discharge rate of 44.9%. The common neonatal morbidities were respiratory distress syndrome, bronchopulmonary dysplasia and sepsis. The majority of neonatal deaths within 24 h post birth were associated with pulmonary hypoplasia, severe intraventricular haemorrhage and neonatal sepsis. The common maternal outcomes were chorioamnionitis and caesarean sections. The major predictors of neonatal survival were later gestational age at PPROM, adequate residual amniotic fluid levels, C-reactive protein <1 mg/dL within 24 h of admission and PPROM after invasive procedures. CONCLUSION: Pregnancy latency and neonatal survival following previable PPROM has improved in recent years, although neonatal morbidity remains unchanged despite recent advances in obstetric and neonatal care. There is heterogeneity in management practices across centres worldwide.

Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study.

BACKGROUND AND AIM: Crohn's disease pathogenesis involves alterations in the gut microbiota. We characterized the mucosa-associated microbiota at the time of surgical resection and 6 months later to identify bacterial profiles associated with recurrence and remission. METHODS: Tissue samples were collected from surgical resection specimens in 12 Crohn's disease patients, and at 6 months postoperative colonoscopy from the neoterminal ileum and anastomosis. Endoscopic recurrence was assessed using the Rutgeerts score. Microbiota was characterized using microarray and 454 pyrosequencing. Longitudinal comparisons were made within patients, and cross-sectional comparisons made with colonoscopic biopsies from the terminal ileum and cecum of 10 healthy subjects. RESULTS: Microbiota of healthy subjects had high diversity and was dominated by the Firmicutes, Bacteroidetes, and Proteobacteria phyla. Biodiversity was lower in Crohn's disease patients at the time of surgery, increased after surgery, but still differed from healthy subjects. Crohn's disease patients with recurrent disease retained a microbiota favoring proteolytic-fueled fermentation and lactic acid-producing bacteria, including Enterococcus and Veillonella spp., while those maintaining remission demonstrated predominant saccharolytic Bacteroides, Prevotella, and Parabacteroides spp., and saccharolytic, butyrate-producing Firmicutes. CONCLUSION: In Crohn's disease, the mucosa-associated microbiota diversity is reduced at the time of surgery, but also differs between patients with different clinical outcomes at 6 months. These findings may provide prognostic information at the time of surgery, allowing identification of patients at increased risk of recurrence, and provide basis for a more targeted approach for therapeutic interventions after surgery.

Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing.

BACKGROUND: The role of bacteriophage in Crohn's disease (CD) is unknown. This study investigated the abundance of phages in ileal and colonic samples from pediatric CD patients and controls. METHODS: Ileal and colonic biopsies from 6 CD patients, gut wash samples from 3 CD patients, and ileal biopsies from 6 noninflammatory bowel disease patients (controls) were analyzed for the presence of bacteriophage using 454 high-throughput pyrosequencing. A sequence-independent single-primer amplification method was used to amplify viral sequences. RESULTS: A total of 186,143 high quality reads were obtained from the 4 sample populations. Contigs and sequence clusters (generated from unassembled singletons) were aligned with sequences from the National Center for Biotechnology Information viral reference database and analyzed by MEGAN. The largest number of viral hits was obtained from the CD gut wash samples (n = 691), followed by CD ileal samples (n = 52), control ileum samples (n = 20), and CD colonic samples (n = 1). The most abundant virus sequences identified belonged to the Caudovirales phage. CONCLUSIONS: Our study characterized a diverse phage community in the gut of CD patients. In this study, we have identified differences in phage composition between CD patients and control individuals. The large abundance of phages in CD ileum tissue and CD gut wash sample suggests a role of phage in CD development. The role of phage dysbiosis in CD is currently unknown but opens up a new area of research.

Current knowledge and systematic review of viruses associated with Crohn's disease.

The aetiology of Crohn's disease (CD) is currently unknown. A viral trigger was proposed more than 40 years ago and has been the focus of many investigations. We summarised the current literature surrounding the association between viruses and CD and conducted a systematic review of all studies investigating this association quantitatively. Studies were identified by searching for 13 specific virus names or the general term 'virus' and 'Crohn's disease' in search engines PubMed and OVID. A total of 1315 studies were identified, of which 78 studies had a laboratory result. Of the 78, 46 case-control studies met all the inclusion criteria for forest plot analysis. The most common viruses studied were EBV, CMV and measles virus (MV). Forest plot analysis for each virus was carried out (fitted using random effects) and identified evidence of an association between CD and CMV (risk ratio [RR] 1.602, 95% confidence interval [CI] 1.069 to 2.400) with some suggestion that EBV may also be associated with CD (RR 1.366, 95% CI 0.996 to 1.873). However, there was evidence of large heterogeneity in the results from the identified studies for EBV. There was little evidence of an association with CD for MV, human herpes virus 6, human herpes virus 8, human simplex virus, varicella-zoster virus, mumps virus, Rubella virus, rotavirus, norovirus and adenovirus. There is still some question around whether CD is associated with the presence of a currently known virus.

Expression profile of genes involved in pathogenesis of pediatric Crohn's disease.

BACKGROUND AND AIM: Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset. METHODS: We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age- and sex-matched controls without inflammatory bowel disease (IBD). RESULTS: Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty-eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real-time reverse transcription polymerase chain reaction performed on ileal-derived RNA from 13 CD and nine non-IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort. CONCLUSION: The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial- and virus-related genes in our CD-patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD.

Interaction of Crohn's disease susceptibility genes in an Australian paediatric cohort.

Genetic susceptibility is an important contributor to the pathogenesis of Crohn's disease (CD). We investigated multiple CD susceptibility genes in an Australian paediatric onset CD cohort. Newly diagnosed paediatric onset CD patients (n = 72) and controls (n = 98) were genotyped for 34 single nucleotide polymorphisms (SNPs) in 18 genetic loci. Gene-gene interaction analysis, gene-disease phenotype analysis and genetic risk profiling were performed for all SNPs and all genes. Of the 34 SNPs analysed, four polymorphisms on three genes (NOD2, IL23R, and region 3p21) were significantly associated with CD status (p<0.05). All three CD specific paediatric polymorphisms on PSMG1 and TNFRSF6B showed a trend of association with p<0.1. An additive gene-gene interaction involving TLR4, PSMG1, TNFRSF6B and IRGM was identified with CD. Genes involved in microbial processing (TLR4, PSMG1, NOD2) were significantly associated either at the individual level or in gene-gene interactive roles. Colonic disease was significantly associated with disease SNP rs7517847 (IL23R) (p<0.05) and colonic and ileal/colonic disease was significantly associated with disease SNP rs125221868 (IBD5) and SLC22A4 & SLC22A4/5 variants (p<0.05). We were able to demonstrate genetic association of several genes to CD in a paediatric onset cohort. Several of the observed associations have not been reported previously in association with paediatric CD patients. Our findings demonstrate that CD genetic susceptibility in paediatric patients presents as a complex interaction between numerous genes.