Effect of oropharyngeal colostrum therapy in the prevention of necrotising enterocolitis among very low birthweight neonates: A meta‐analysis of randomised controlled trials

Background

Necrotising enterocolitis (NEC ) is one of the most common life‐threatening emergencies of the gastrointestinal tract in preterm neonates. The present study aimed to determine the efficacy of oropharyngeal colostrum with respect to reducing NEC in preterm neonates.

Methods

A literature search was conducted for various randomised control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE and ongoing clinical trials. Randomised or quasi‐randomised trials comparing oropharyngeal colostrum versus placebo in neonates (birthweight ≤ 1500 g or gestational age ≤ 32 weeks) were included in the review. The methodological quality of each trial was independently reviewed by the authors. For categorical and continuous variables, typical estimates for relative risk and typical estimates for weighted mean difference were calculated, respectively. A random effect model was assumed for meta‐analysis.

Results

In total, four eligible trials were included in the review. Oropharyngeal colostrum therapy was not associated with a statistically significant reduction in the incidence of NEC stage ≥2 [typical relative risk (RR ) = 0.64; 95% confidence interval (CI ) = 0.27–1.49], mortality from any cause (typical RR  = 0.86; 95% CI  = 0.15–4.80) and time to reach full feed [typical weighted mean difference (WMD) = ?3.26; 95% CI  = ?8.87 to 2.35]. Duration of hospital stay was significantly less in the control group (typical WMD  = 9.77; 95% CI  = 3.96–15.59).

Conclusions

The current evidence is insufficient for recommending oropharyngeal colostrum as a routine clinical practice in the prevention of NEC . We emphasise the need for large randomised controlled trials with an adequate sample size and validated clinical outcomes in preterm neonates.

     

Recent Insights into Clostridium perfringens Beta-Toxin

Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.     

Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthritis: A possible manifestation of methotrexate hypersensitivity

Summary Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluo-rescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.     

Glutamine downregulates TLR-2 and TLR-4 expression and protects intestinal tract in preterm neonatal rats with necrotizing enterocolitis

Background/Purpose

Toll-like receptor (TLR)-4 and TLR-2 play an essential role in the pathogenesis of necrotizing enterocolitis (NEC). In this study, we investigated the protective effect of glutamine (Gln) in an NEC neonatal rat model, and the potential association with TLR-4 and TLR-2 expression in local intestinal tissues.

Methods

Preterm neonatal rats were randomly divided into 3 groups: normal control; NEC model; and NEC plus Gln intervention. NEC was induced by feeding with artificial milk substitutes, plus exposure to hypoxia and cold stress. All preterm rats were sacrificed at 3 days after birth. The intestinal tissues were taken for pathological analysis. Protein and mRNA expression of TLR-2, TLR-4, and caspase-3 was examined by immunohistochemistry and real-time RT-PCR, respectively.

Results

Compared with the normal control, the NEC neonatal rats showed mucosal injury and upregulated mRNA and protein expression of TLR-2, TLR-4, and caspase-3 in ileum and colon. Gln intervention significantly reduced the mucosal injury and suppressed the upregulated expression of TLR-2, TLR-4, and caspace-3 in the ileum and colon of NEC neonatal rats.

Conclusions

Gln protects the intestinal tract of NEC neonatal rats, which may be associated with the reduction of TLR-2 and TLR-4 expression in intestines     

影响新生儿坏死性小肠结肠炎严重程度的危险因素

[摘要]目的：探讨影响新生儿坏死性小肠结肠炎（NEC）患儿疾病严重程度的危险因素。方法：采用回顾性研究,选择2010年1月至2016年5月在我院新生儿中心住院的新生儿,符合NEC诊断且Bell分期≥Ⅱ期。采用单因素分析和二元Logistic回归分析,讨论NEC严重程度相关的危险因素。结果：本研究共纳入197例新生儿,其中NEC Ⅱ期组121例,Ⅲ期组76例;单因素分析结果表明：胎龄、发病日龄、溶血症、败血症、CRP>8 mg/L、休克、血小板减少症、确诊前胃肠减压的时间两组比较差异均有统计学意义（P<0.05）;将单因素分析提示差异有统计学意义的变量,进一步进行二元Logistic回归分析,得到发病日龄（OR：0.958,95% CI：0.927,0.991,P<0.05）、胎龄（OR：0.872,95% CI：0.784,0.971,P<0.05）和确诊前胃肠减压的时间（OR：1.377,95%CI：1.054-1.801,P<0.05）为影响NEC严重程度的危险因素。结论：发病日龄及胎龄越小、确诊前胃肠减压的时间越长的患儿越容易发展至NEC Ⅲ期。因此应高度重视胎龄小的NEC患儿,缩短胃肠减压的时间,以降低NEC患儿病情的严重程度。     

Modulation of Intestinal Inflammation by Minimal Enteral Nutrition With Amniotic Fluid in Preterm Pigs

Background: Necrotizing enterocolitis (NEC) is a severe inflammatory disorder, associated with the difficult transition from parenteral to enteral feeding after preterm birth. We hypothesized that minimal enteral nutrition (MEN) with amniotic fluid (AF), prior to enteral formula feeding, would improve resistance to NEC in preterm pigs. Methods: Experiment 1: IEC‐6 cells were incubated with porcine (pAF) and human AF (hAF) to test AF‐stimulated enterocyte proliferation and migration in vitro. Experiment 2: Cesarean‐delivered, preterm pigs were fed parenteral nutrition and MEN with pAF, hAF, or control fluid (MEN‐pAF, MEN‐hAF, or MEN‐CTRL; all n = 9) for 2 days before tissue collection. Experiment 3: Preterm pigs were fed MEN diets as in experiment 2, but followed by 2 days of enteral formula feeding, which predisposes to NEC (NEC‐pAF, NEC‐hAF, or NEC‐CTRL; n = 10–12). Results: Both pAF and hAF stimulated enterocyte proliferation and migration in vitro. In experiment 2, MEN‐pAF and MEN‐hAF pigs showed increased body weight gain and reduced intestinal interleukin (IL)–8 and colonic IL‐6 levels, indicating reduced inflammatory response. In experiment 3, body weight gain was highest in the 2 groups fed AF as MEN, but NEC incidences were similar (NEC‐pAF) or increased (NEC‐hAF) compared with controls. Conclusions: Intake of pAF or hAF improved body growth and modulated intestinal inflammatory cytokines during a period of parenteral nutrition, but did not protect against later formula‐induced NEC in preterm pigs. Further studies are required to show if MEN feeding with species‐specific AF, combined with an optimal enteral diet (eg, human milk), will improve adaptation during the transition from parenteral to enteral feeding in preterm neonates.