Multi-modal approach to prophylaxis of necrotizing enterocolitis: clinical report and review of literature

For the first time a multimodal approach to NEC prophylaxis is reported, consisting of early trophic feeding with human breast milk, and enteral administration of an antibiotic, an antifungal agent, and probiotics. A retrospective analysis of local protocol of NEC prophylaxis is presented. Included were all VLBWI admitted to the NICU, including transfers within the first 28 days of life. These infants were divided into two groups, an “inborn group” (infants admitted within the first 24 h of life) and an “outborn group” (infants admitted after the onset of their second day of life). Prophylaxis of NEC according to protocol was started at the day of admission, and was continued until discharge. Between 1998 and 2004, 405 VLBWI were admitted, including all transfers within the first 28 days of life. A total of 334 (82%) infants were admitted within the first 24 h of life (inborn group), and 71 (18%) were admitted after 24 h of life (outborn group). Five infants developed clinical features of necrotizing enterocolitis. The inborn group showed a NEC incidence of 0.7% (two infants), whereas the outborn group showed a NEC incidence of 4.5% (three infants), respectively. This difference was significant (P=0.049, Fisher’s exact test). A surgical treatment with bowel resection was performed in two infants (both from the outborn group). The present study used a combination of different strategies, all having shown to have some beneficial effect, but not having brought a clinical breakthrough in single administration studies. Combinated were the beneficial effects of human breast milk feeding, oral antiobiotics, oral antifungal agents, and the administration of probiotics. In a homogenous group of preterm infants, using this protocol of multimodal NEC prophylaxis, there was a very low incidence of NEC, when started within the first 24 h of life.     

Neonatal necrotizing enterocolitis: An update

Necrotizing enterocolitis (NEC) is a leading cause of mortality and morbidity in neonatal intensive care units. Here we review selected manifestations of NEC, risk factors involved in its pathophysiology as well as putative mechanisms associated with how an immature gut might be more susceptible to NEC. Treatment and potential preventive strategies are discussed.     

Neonatal necrotizing enterocolitis: an update

Necrotizing enterocolitis (NEC) is a leading cause of mortality and morbidity in neonatal intensive care units. Here we review selected manifestations of NEC, risk factors involved in its pathophysiology as well as putative mechanisms associated with how an immature gut might be more susceptible to NEC. Treatment and potential preventive strategies are discussed.     

Enteric fistula formation secondary to necrotizing enterocolitis

We report two cases of enterocolonic fistula formation following necrotizing enterocolitis, and a review of the six previously published cases. Ischemic mechanism is the most likely cause. The fistulas were diagnosed by upper gastrointestinal series and contrast enema.     

Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22-28 wk GA. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation, and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD+) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 overactivation may ensue, depleting cells of NAD+ and ATP, killing them by metabolic catastrophe. Here, we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage) versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3-4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 overactivation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC.     

Pericholecystic hyperechogenicities in necrotizing enterocolitis: A specific sonographic sign

The authors report a new sonographic pattern found in association with neonatal necrotizing enterocolitis in 5 newborns: hyperechogenicities around the gallbladder. The pattern probably corresponds to extension of the disease to the perivesicular space. The most probable hypothesis for that extension is diffusion by contiguity through the lesser sac and/or the right gutter. The hyperechogenicities could be related to the foamy infiltrate typical of NEC. Air within the pericholecystic vascular system similar to portal air could be another (less probable) explanation.Presented at the ESPR meeting in Munich 1990. Selected for publication by an International Group of the ESPR     

Surgical therapy for necrotizing enterocolitis: bringing evidence to the bedside

Necrotizing enterocolitis is the most common surgical emergency in the neonatal intensive care unit. Despite decades of research that have led to a growing knowledge base about this disease, NEC continues to challenge the pediatric surgeon. In this review, we will examine the development of surgical therapy for NEC in the context of the supportive evidence, or lack thereof, for treatment approaches. We will discuss issues of indications for surgical intervention, primary peritoneal drainage versus laparotomy, enterostomy versus primary anastamosis and issues surrounding NEC totalis.     

Primary anastomosis in necrotizing enterocolitis: the first option to consider

Introduction

Necrotizing enterocolitis (NEC) is the most frequent gastrointestinal emergency in preterm newborns. Thirty percent of all cases will require surgical intervention. Following resection of the involved segment, most patients will undergo a diverting enterostomy.

Objective

To describe the safety and effectiveness of primary anastomosis in patients with complicated NEC.

Methods

This study was a retrospective chart review. The study participants were obtained from both public and private health systems between December 2004 and December 2009 in Santiago, Chile. The inclusion criteria were any patient who underwent a laparotomy for necrotizing enterocolitis. The following variables were evaluated: gestational age, birth weight, use of peritoneal drains, macroscopic features of the intestinal segment, number of anastomoses, parenteral nutrition requirements and post-surgical complications.

Results

Seventy patients were identified. Sixty patients (85?%) underwent primary anastomosis. The remaining 10 patients underwent a resection with enterostomy. In the primary anastomosis group (n?=?60), twelve percent weighed <1,000?g and 22?% weighed 1,000–1,500?g. Two anastomoses were required in 18 patients. Post-surgical complications included infection of the surgical wound in three cases and anastomotic dehiscence in only one case. Seven percent developed short bowel syndrome. Overall mortality was 11.6?%, all secondary to sepsis.

Conclusion

In this series, primary anastomosis was a safe alternative in the management of complicated NEC, with low morbidity and mortality, independent of age, weight, intraperitoneal contamination or extent of disease.     

A critical analysis of risk factors for necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most common serious gastrointestinal morbidity in preterm infants. A number of risk factors for NEC have been reported in the literature. With the exception of decreasing gestational age, decreasing birth weight and formula feeding, there is disagreement on the importance of reported risk factors with uncertain causality. Causal risk factors may be observed at any time before the onset of NEC, including prior to an infant's birth. The purpose of this review is to examine the existing literature and summarize risk factors for NEC. This review may be helpful in understanding the epidemiology of NEC and inform the measurement and assessment of risks factors for NEC in research studies and quality improvement projects.     

Intestinal atresia and necrotizing enterocolitis: Embryology and anatomy

The primitive gut originates at week 3 of gestation from the endoderm, with posterior incorporation of the remaining embryo layers. Wnt, Notch and TLR4 pathways have been shown to play central roles in the correct development of the intestine. The classical hypothesis for intestinal atresia development consists of failure in bowel recanalization or a vascular accident with secondary bowel reabsorption. These have been challenged due to the high frequency of associated malformations, and furthermore, with the discovery of molecular pathways and genes involved in bowel formation and correlated defects producing atresia.Necrotizing enterocolitis (NEC) has a multifactorial pathogenesis with prematurity being the most important risk factor; therefore, bowel immaturity plays a central role in NEC. Some of the same molecular pathways involved in gut maturation have been found to correlate with the predisposition of the immature bowel to develop the pathological findings seen in NEC.     

影响新生儿坏死性小肠结肠炎预后的危险因素分析

目的探讨影响新生儿坏死性小肠结肠炎(neonatal necrotizing enterocolitis,NEC)预后的危险因素.方法对1990年4月至2003年4月收治156例NEC患儿进行回顾性分析.结果早产儿41例,足月儿110例,过期产儿5例.发病时间≤3d 94例,>3d 62例.治愈66例(42.3%),好转39例(25%),放弃14例(9%),死亡37例(23.7%).单因素分析发现NEC患儿病死组较治愈组合并或并发败血症、硬肿症、呼吸衰竭、全腹膜炎、颅内出血、代谢性酸中毒、低钠血症、肺出血、全心衰、肾功能衰竭、休克、中毒性脑病者发生率高,P<0.05.治愈组白细胞≤5×109/L或≥20×109/L为21.2%(14/66),病死组为45.9%(17/37),χ2=6.894,P<0.01.治愈组血小板计数(PLT)≤100×109/L发生率为18.2%(12/66),病死组为59.5%(22/37),χ2=18.268,P<0.001.治愈组腹部X线Ⅰ、Ⅱ、Ⅲ期表现发生率分别为74.2%、18.2%、7.6%,病死组分别为40.5%、24.3%、35.1%,χ2=15.077,P<0.0017.回归方程Logistic(NEC)=-2.1452+1.2971X2+1.6557X7+1.7707X10+1.7825X12+3.2555X15(χ2=24.5953,P<0.001).Logistic回归分析显示全腹膜炎、新生儿硬肿症、低钠血症、PLT≤100×109/L、呼吸衰竭的OR值分别为3.659、5.237、5.875、5.981、25.933(P<0.05).结论全腹膜炎、新生儿硬肿症、低钠血症、PLT≤100×109/L、呼吸衰竭为影响NEC预后的危险因素,积极防治NEC各种合并症及并发症,有助于降低其病死率.     

A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy

In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.     

Tissue engineering and organ structure: a vascularized approach to liver and lung

Over the past two decades, great strides have been made in the field of tissue engineering. Many of the initial attempts to develop an engineered tissue construct were based on the concept of seeding cells onto an avascular scaffold. Using advanced manufacturing technologies, the creation of a preformed vascular scaffold has become a reality. This article discusses some of the issues surrounding the development of such a vascular scaffold. We then examine of the challenges associated with applying this scaffold technology to two vital organ constructs: liver and lung.