Does red blood cell irradiation and/or anemia trigger intestinal injury in premature infants with birth weight ≤ 1250 g? An observational birth cohort study

BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality in premature infants. To date, no effective biomarkers exist to predict which premature infants will develop NEC, limiting targeted prevention strategies. Multiple observational studies have reported an association between the exposure to red blood cell (RBC) transfusion and/or anemia and the subsequent development of NEC; however, the underlying physiologic mechanisms of how these factors are independently associated with NEC remain unknown. METHODS: In this paper, we outline our prospective, multicenter observational cohort study of infants with a birth weight ≤ 1250 g to investigate the associations between RBC transfusion, anemia, intestinal oxygenation and injury that lead to NEC. Our overarching hypothesis is that irradiation of RBC units followed by longer storage perturbs donor RBC metabolism and function, and these derangements are associated with paradoxical microvascular vasoconstriction and intestinal tissue hypoxia increasing the risk for injury and/or NEC in transfused premature infants with already impaired intestinal oxygenation due to significant anemia. To evaluate these associations, we are examining the relationship between prolonged irradiation storage time (pIST), RBC metabolomic profiles, and anemia on intestinal oxygenation non-invasively measured by near-infrared spectroscopy (NIRS), and the development of NEC in transfused premature infants. DISCUSSION: Our study will address a critical scientific gap as to whether transfused RBC characteristics, such as irradiation and metabolism, impair intestinal function and/or microvascular circulation. Given the multifactorial etiology of NEC, preventative efforts will be more successful if clinicians understand the underlying pathophysiologic mechanisms and modifiable risk factors influencing the disease. TRIAL REGISTRATION: Our study is registered in ClinicalTrials.gov Identifier: NCT02741648.