Transfusion Related Necrotizing Enterocolitis in Premature Infants Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality with a poorly understood pathogenesis. The disease is characterized by the rapid development of intestinal inflammation, often leading to intestinal necrosis. Currently, there is n safe and effective treatment to prevent NEC. Multiple recent studies have identified red blood cell (RBC) transfusion, a common therapy in very low birth weight (VLBW) premature infants for the treatment of anemia, as an important risk factor and potential causative factor in the development of NEC. While a compelling factor in the etiology of NEC, the clinical determinants of RBC transfusion-related NEC remain poorly understood. The applicant, Dr. Ravi Mangal Patel, will bring to bear expertise from national leaders in transfusion medicine (primary mentor: Dr. Cassandra Josephson), neonatal medicine (co-mentor: Dr. David Carlton) and necrotizing enterocolitis (co-mentor: Dr. Patricia Denning) to better understand how donor RBC factors contribute to NEC and how probiotic therapy may protect against NEC. Specifically, this proposal aims to determine the effect of Lactobacillus rhamnosus GG on intestinal oxygenation in transfused VLBW infants using near infrared spectroscopy and understand if repeated RBC transfusions from the same single blood unit is a risk factor for NEC. This proposal will capitaliz on the unique opportunity provided by recently collected data from a completed prospective, multicenter birth cohort study and an upcoming prospective study, both funded by the NHLBI and led by Dr. Josephson (primary mentor). This mentored research experience will allow Dr. Patel, a neonatologist with a strong commitment to patient- oriented research who received a Master of Science in Clinical Research as a NIH KL2 scholar, to pursue additional advanced mentored clinical research training pertaining to the execution of large, complex clinical studies. Dr. Patel's long-term career goal is to advance public health and neonatal care through clinical investigation into prevention strategies and interventions to decrease morbidity and mortality caused by NEC. Dr. Patel plans to achieve this through multicenter, collaborative clinical trials coupled with investigator initiated observational studies (R01/U01). The candidate's short-term career goals are to: 1) develop broad expertise in neonatal transfusion medicine; 2) develop expertise in conducting prospective observational research; 3) obtain the skills necessary to successfully develop, design and execute a multicenter clinical trial; 4) become proficient in the use of near infrared spectroscopy; 5) develop skills in longitudinal data analysis and clinical tril methodology. The mentored research training will provide Dr. Patel with new expertise in transfusion medicine and new skills in advanced biostatistics, epidemiology and clinical trial design. This will prepare him for an independent clinical research career focused on developing interventions to reduce NEC and other devastating complications of prematurity.
Red Cell Transfusion, Severe Anemia, and Necrotizing Enterocolitis This proposal aims to improve our understanding of necrotizing enterocolitis (NEC), a devastating complication of prematurity. This includes investigating the role of blood transfusion practices and identifying how probiotics may reduce the risk of NEC in preterm infants. The public health impact of the new knowledge gained at the completion of this study will be high, as 20-30% of infants with NEC die, and NEC remains the most common gastrointestinal emergency in preterm infants. This results in a significant financial burden, with the cost of care for affected infants in the United States estimated to be up to $1 billion per yea.
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