Vitamin A in the treatment of neonatal necrotizing enterocolitis

维生素A治疗新生儿坏死性小肠结肠炎

• 批准号: 7131027
• 负责人: CHRISTIAN L COLES
• 金额: $ 11.49万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7131027
• 关键词: Bangladesh; clinical research; cost effectiveness; dietary supplements; gene induction /repression; human subject; human therapy evaluation; infant mortality; inflammation; interferon gamma; interleukin 10; interleukin 4; interleukin 8; international cooperation; longitudinal human study; necrotizing enterocolitis; newborn human (0-6 weeks); nutrition related tag; pathologic process; patient care management; patient oriented research; platelet activating factor; premature infant human; retinoids; tumor necrosis factor alpha; vitamin A deficiency

DESCRIPTION (provided by applicant): Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in newborns, particularly in preterm infants. In industrialized countries, earlier diagnosis and advances in neonatal critical care have improved survival. In developing countries, improved survival of low birth weight infants is being accompanied by an increase in NEC cases without parallel improvement in management due to resource constraints. Research on affordable interventions to improve NEC outcomes is needed. Vitamin A (VA), typically low in preterm infants, is an essential nutrient for maintaining gut integrity, immune competence and other host defenses. Experimental VA deficiency produces lesions in the gut and changes in immunity similar to those caused by NEC. It is plausible that reductions in early infant death following newborn VA receipt of high-potency VA, as reported from South Asia, may have been mediated, in part, by enhanced protection against NEC. Thus, a relevant question is whether VA can improve NEC outcomes in undernourished populations. To address this question, we propose to conduct a randomized, double-blinded, placebo-controlled VA supplementation trial in Bangladesh, at the Shishu Children's Hospital in Dhaka, a national pediatric referral center. The aims are to evaluate the efficacy of VA supplementation in: 1) reducing inflammatory cytokine expression; 2) ameliorating severity and duration of symptoms; and 3) decreasing risks of disease progression and mortality in newborns with NEC. Quantifying these pathways and effects of VA may help to improve treatment efficacy and provide new insights to preventing NEC in developing countries. The study builds on clinical trial research currently underway between Johns Hopkins University (JHU) and Shishu Hospital. The study is proposed as part of a K01 award to prepare the PI as an independent investigator in nutritional immunology. The PI candidate will be guided by Drs. West, Bream, and Bourgeois at JHU, who will work with him through combined directed readings, coursework, laboratory training in nutrition, microbiology and immunology, training in clinical trial conduct, and supervising his international, collaborative research. In the short term, the candidate will gain skills to characterize interactions of VA, infection and cytokine expression through laboratory and field investigation, while the study contributes evidence on the potential roles of VA in treating and preventing severe pediatric diseases associated with malnutrition.

描述（由申请人提供）： 坏死性小肠结肠炎（NEC）是新生儿（尤其是早产儿）胃肠道疾病死亡的主要原因。在工业化国家，早期诊断和新生儿重症监护的进步提高了生存率。在发展中国家，低出生体重婴儿生存率的提高伴随着 NEC 病例的增加，但由于资源限制，管理方面却没有相应改善。需要对可负担的干预措施进行研究，以改善 NEC 的结果。维生素 A (VA) 在早产儿中通常含量较低，但它是维持肠道完整性、免疫能力和其他宿主防御的必需营养素。实验性 VA 缺乏会导致肠道损伤和免疫力变化，类似于 NEC 引起的情况。据南亚报道，新生儿 VA 接受高效 VA 后早期婴儿死亡的减少可能部分是通过增强对 NEC 的保护来介导的。因此，一个相关问题是 VA 是否可以改善营养不良人群的 NEC 结局。为了解决这个问题，我们建议在孟加拉国达卡的 Shishu 儿童医院（国家儿科转诊中心）进行一项随机、双盲、安慰剂对照的 VA 补充试验。目的是评估补充 VA 在以下方面的功效：1) 减少炎症细胞因子的表达； 2) 改善症状的严重程度和持续时间； 3) 降低 NEC 新生儿疾病进展和死亡的风险。量化 VA 的这些途径和作用可能有助于提高治疗效果，并为发展中国家预防 NEC 提供新见解。该研究建立在约翰·霍普金斯大学 (JHU) 和师树医院目前正在进行的临床试验研究的基础上。该研究被提议作为 K01 奖项的一部分，以帮助 PI 成为营养免疫学的独立研究者。 PI 候选人将由 Drs 指导。约翰霍普金斯大学的韦斯特、布里姆和布尔乔亚将与他合作，通过综合定向阅读、课程作业、营养学、微生物学和免疫学实验室培训、临床试验实施培训以及监督他的国际合作研究。短期内，候选人将通过实验室和现场调查获得表征 VA、感染和细胞因子表达相互作用的技能，同时该研究为 VA 在治疗和预防与营养不良相关的严重儿科疾病中的潜在作用提供证据。