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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Mondoro, Traci
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Emory University
Schools of Medicine
United States
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Roberts, Jessica L; Patel, Ravi M (2017) Antibiotic utilisation in very low birth weight infants without sepsis or necrotising enterocolitis is associated with multiple adverse outcomes. Evid Based Med 22:187
Patel, Ravi Mangal (2017) Does fluconazole prophylaxis reduce death or invasive candida infection in extremely preterm infants? Acta Paediatr 106:844-845
Patel, Ravi Mangal (2017) Does early treatment with inhaled budesonide prevent death or bronchopulmonary dysplasia in extremely preterm infants? Acta Paediatr 106:683
Denning, Timothy L; Bhatia, Amina M; Kane, Andrea F et al. (2017) Pathogenesis of NEC: Role of the innate and adaptive immune response. Semin Perinatol 41:15-28
Pakvasa, Mitali A; Winkler, Anne M; Hamrick, Shannon E et al. (2017) Observational study of haemostatic dysfunction and bleeding in neonates with hypoxic-ischaemic encephalopathy. BMJ Open 7:e013787
Patel, Ravi M; Zimmerman, Kanecia; Carlton, David P et al. (2017) Early Caffeine Prophylaxis and Risk of Failure of Initial Continuous Positive Airway Pressure in Very Low Birth Weight Infants. J Pediatr 190:108-111.e1
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Patel, Ravi Mangal; Rysavy, Matthew A; Bell, Edward F et al. (2017) Survival of Infants Born at Periviable Gestational Ages. Clin Perinatol 44:287-303
Patel, Ravi Mangal; Meyer, Erin K; Widness, John A (2016) Research Opportunities to Improve Neonatal Red Blood Cell Transfusion. Transfus Med Rev 30:165-73
Higgins, Rosemary D; Patel, Ravi Mangal; Josephson, Cassandra D (2016) Preoperative Anemia and Neonates. JAMA Pediatr 170:835-6

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