NEONATAL SURGICAL DATABASE: NECROTIZING ENTEROCOLITIS (NEC) PROTOCOL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。儿科外科医生经常治疗患有罕见疾病的儿童。对于新生儿外科疾病，如坏死性小肠结肠炎，尤其如此。即使是一个主要的儿科转诊中心也不会看到足够数量的患者来有意义地评估该机构治疗方法的结果。由于这个原因，关于NEC患儿护理的科学文献几乎完全由轶事病例报告和单一机构病例系列数据组成。这项研究由格拉泽儿科研究网络赞助。Glaser研究网络成立于2001年，旨在协调6个机构（贝勒大学、哈佛大学、旧金山大学、斯坦福大学、南加州大学、加州大学洛杉矶分校）之间的数据收集。通过结合这6个机构的数据，可以进行更有意义的分析。坏死性小肠结肠炎是一种严重的肠道炎症性疾病，发生在早产儿和低出生体重儿。NEC在20世纪60年代首次被描述，现在是新生儿中最常见的外科急诊。据报道，NEC的发病率为新生儿重症监护病房（NICU）入院人数的1%至5%，或每1000例活产1至3例。根据国家卫生统计中心和多中心试验的数据分析，美国每年约有10,000例NEC病例。这导致每年大约2500人死亡。NEC的发病率与早产程度密切相关。正是这些出生体重非常低的婴儿给医生带来了最大的临床挑战。由于NEC的成功治疗通常会导致儿童能够过上健康和充分生产的生活，因此护理方面的改进可以在挽救生命的年数方面产生巨大影响。NEC的临床表现可以从喂养不耐受到严重败血症合并心血管衰竭。NEC没有明确的治疗方法。大多数病例对停止口服喂养、鼻胃减压、液体复苏、广谱抗生素和其他支持措施有反应。严重的NEC可导致肠道坏死和穿孔。当这些情况发生时，手术干预是必要的。识别具有特定NEC发展风险的婴儿是一个尚未解决的挑战。很明显，NEC的发病率与早产程度密切相关。在20世纪60年代，只有少数NEC患者被报道，当时极低出生体重（VLBW）婴儿存活的时间不够长，无法患上这种疾病。常规使用产前类固醇和预防性表面活性剂导致更多的VLBW婴儿存活。正是这些极度早产的婴儿在NEC的临床管理中给医生带来了最大的挑战。除了早产，NEC的其他危险因素还不太明确。自1978年以来，肠内喂养被认为是NEC的一个原因。25年来，新生儿学家一直主张对早产儿进行缓慢而谨慎的喂养。在缺乏可靠数据的情况下，这种信念导致了无数不同喂养方法的发展。最近的一项随机试验无法显示接受缓慢或快速肠内喂养的婴儿在NEC发生率上的差异。这项小型试验的结果与其他非随机数据形成对比，表明饲料的缓慢推进可以预防NEC。一个类似的未解决的问题是，与配方奶相比，母乳喂养是否会减少NEC的发病率。几项小型和不受控制的研究提供了相互矛盾的结果。与NEC发病机制有关的其他危险因素包括青紫型先天性心脏病、动脉导管未闭、呼吸暂停和心动过缓、先前的败血症发作和各种其他异常。许多流行病学研究未能找到除早产以外的一致的风险预测因素。一旦诊断为NEC，标准的做法是制定肠道休息，胃减压，和广谱抗生素。许多患者对这种治疗反应良好，无需进一步干预即可康复。另一些则恶化并发展为肠坏死或穿孔，需要紧急手术。几乎没有证据表明哪些因素可以帮助预测哪些婴儿最有可能恶化。到目前为止，还没有大型前瞻性研究跟踪诊断为NEC的婴儿并确定其病程。识别恶化的危险因素可以使更密集的治疗集中在那些最有可能受益的人身上。此外，这些数据可以让那些没有高风险的人更快地恢复肠内喂养和常规新生儿护理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pediatric surgeons often care for children with uncommon diseases. This is particularly true of major neonatal surgical disorders such as Necrotizing Enterocolitis. Even a major pediatric referral center will not see an adequate number of patients to meaningfully assess outcomes from the institution's treatment approach. For this reason, the scientific literature on the care of children with NEC is almost exclusively comprised of anecdotal case reports and single-institution case-series data. This study is sponsored by the Glaser Pediatric Research Network. The Glaser Research Network was established in 2001 to coordinate data collection between 6 institutions (Baylor, Harvard, University of San Francisco, Stanford, USC, UCLA). By combining data from these 6 institutions a more meaningful analysis can be carried out. Necrotizing Enterocolitis is a severe inflammatory disease of the intestine that occurs in premature and low birth weight infants. First described in the 1960s, NEC is now the most common surgical emergency in the newborn infant. The incidence of NEC is reported to be from 1% to 5% of neonatal intensive care unit (NICU) admissions or 1 to 3 cases per 1,000 live births. Based upon analysis of data from the National Center for Health Statistics and multi-center trials, there are about 10,000 cases of NEC per year in the United States. This results in approximately 2500 deaths per year. The incidence of NEC correlates strongly with the degree of prematurity. It is these very low birth weight babies which present the physician with the greatest clinical challenge. Since successful treatment of NEC typically results in the child being able to lead a healthy and fully productive life, improvements in care can produce a tremendous impact in terms of number of years of life saved. The clinical presentation of NEC can range from feeding intolerance to severe sepsis with cardiovascular collapse. No definitive treatment for NEC exists. Most cases respond to discontinuation of oral feedings with nasogastric decompression, fluid resuscitation, broad-spectrum antibiotics, and other supportive measures. Severe NEC can result in intestinal necrosis and perforation. When these conditions occur, surgical intervention is necessary. Identifying infants at particular risk for the development of NEC is an unsolved challenge. It is clear that the incidence of NEC correlates strongly with the degree of prematurity. Only a handful of patients with NEC were reported in the 1960's when very low birthweight (VLBW) infants did not survive long enough to acquire the disease. The routine use of both antenatal steroids and prophylactic surfactant has resulted in greater numbers of VLBW babies surviving. It is these extremely premature babies that present physicians the greatest challenge in the clinical management of NEC. Beyond prematurity, additional risk factors for NEC are less well defined. Enteral feeding has been implicated as a cause of NEC since 1978. For 25 years, neonatologists have argued for slow and cautious advancement of feeds in premature infants. This belief has led to the development of a myriad of different feeding practices, in the absence of reliable data. A recent randomized trial was not able to show a difference in the rate of NEC between babies receiving slow or rapid advancement of enteral feedings. The results of this small trial contrasts with other non-randomized data suggesting that slow advancement of feeds protects against NEC. A similar unsolved question is whether or not breast milk feeding reduces the incidence of NEC compared to formula feeding. Several small and uncontrolled studies have provided conflicting results.Other risk factors implicated in the pathogenesis of NEC include cyanotic congenital heart disease, patent ductus arteriosus, apnea and bradycardia, prior episodes of sepsis and a variety of other abnormalities. Numerous epidemiologic studies have failed to find consistent predictors of risk other than prematurity. Once the diagnosis of NEC is made, standard of practice is to institute bowel rest, gastric decompression, and broad spectrum antibiotics. Many patients respond well to this treatment and recover with no further intervention. Others deteriorate and develop intestinal necrosis or perforation requiring urgent operation. There is little available evidence to suggest what factors may help predict which infants are most likely to deteriorate. To date, no large prospective studies have followed infants diagnosed with NEC and determined their course. Identification of risk factors for deterioration could allow more intensive therapy to be focused on those most likely to benefit. In addition, such data could allow a more rapid return to enteral feeding and routine neonatal care for those not at high risk.