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）是新生儿胃肠道疾病死亡的主要原因，特别是在早产儿中。在工业化国家中，较早的诊断和新生儿重症监护的进展提高了生存。在发展中国家，低出生体重婴儿的生存率提高，伴随着NEC病例的增加，而由于资源限制而没有平行改善管理。需要研究负担得起的干预措施以改善NEC结果。维生素A（VA）通常在早产儿中低，是维持肠道完整性，免疫能力和其他宿主防御能力的必不可少的营养。实验VA缺乏会在肠道中产生病变，并与NEC引起的免疫变化相似。正如南亚报道的，新生儿VA收到高功率VA后，婴儿早期死亡的减少是合理的，可能部分是通过增强对NEC的保护来调节的。因此，一个相关的问题是VA是否可以改善营养不良人群中的NEC结果。为了解决这个问题，我们建议在孟加拉国，在孟加拉国，在国家儿科转诊中心的达卡的Shishu儿童医院进行随机，双盲，安慰剂对照的补充试验。目的是评估补充VA的功效：1）降低炎症性细胞因子的表达； 2）减轻症状的严重程度和持续时间； 3）NEC新生儿中疾病进展和死亡率的风险降低。量化VA的这些途径和影响可能有助于提高治疗效果，并为防止发展中国家的NEC提供新的见解。这项研究基于约翰·霍普金斯大学（JHU）和Shishu医院目前正在进行的临床试验研究。该研究是作为K01奖的一部分提出的，以准备PI作为营养免疫学领域的独立研究者。 PI候选人将由Drs指导。 JHU的West，Bream和Bourgeois将通过有指导的读物，课程，营养，微生物学和免疫学，临床试验培训以及监督其国际协作研究的合并，与他合作。在短期内，候选人将通过实验室和现场调查来表征VA，感染和细胞因子表达的相互作用的技能，而研究则有助于证据证明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。