RBC Irradiation, Anemia and Gut Injury (RBC-mNIRS)

Red Blood Cell Transfusion and Digestive Tract Oxygenation in Preterm Infants Weighing ≤ 1250 Grams

The purpose of this trial is to study the effect that anemia and red blood cell (RBC) transfusions have on oxygen levels in the digestive tracts of extremely low birth weight (ELBW) infants and to look for possible markers in a baby's blood, urine and/or stool that may lead to a better understanding of what makes an ELBW infant at risk for digestive tract problems such as necrotizing enterocolitis.

Study Overview

• Status: Completed
• Conditions: Anemia; Necrotizing Enterocolitis
• Intervention / Treatment: Device: Near Infrared Spectroscopy; Other: Non-invasive Image-based Anemia Assessment

Detailed Description

Necrotizing Enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality in preterm infants. To date, no effective genetic or clinical markers exist to predict which premature infant will develop NEC, limiting targeted prevention strategies. Anemia and digestive tract complications are common problems in extremely low birth weight infants. Anemia is a condition in which the body does not have enough red blood cells (RBC). RBCs are important because they contain hemoglobin, the substance that carries oxygen throughout the body. Transfusions of RBCs in these infants is frequently required to correct the anemia.

Multiple observational studies have reported an association between the exposure to red blood cell (RBC) transfusion and the subsequent development of transfusion related-NEC (TR-NEC).However, no clinical studies have investigated the underlying pathophysiologic mechanisms of TR-NEC. In adults, prolonged RBC storage prior to transfusion has been associated with adverse outcomes and may also contribute to TR-NEC. However, the chronological storage age of blood may not be an accurate gauge of donor RBC function; irradiation of RBCs to prevent transfusion-associated graft-vs-host disease may also contribute to TR-NEC. Currently, the duration considered safe for RBC storage following irradiation (irradiation storage time (IST)) is unclear. Given the multifactorial etiology of NEC, preventative efforts will be more successful if clinicians understand the underlying pathophysiologic mechanisms and modifiable risk factors.

In this study the researchers will conduct a multicenter observational cohort study of very preterm (VPT) infants weighing ≤1250g at birth to prospectively investigate the associations between RBC transfusion, digestive tract oxygenation, and TR-NEC. The overarching hypothesis for this study is that irradiation of RBC units followed by prolonged storage perturbs RBC metabolism and function, and these derangements are associated with paradoxical microvascular vasoconstriction, tissue hypoxia and TR-NEC in transfused infants with already impaired gut oxygenation due to significant anemia. All RBC units transfused to VPT infants throughout the study will be stored based on current standard operating procedures per local site blood banking practices. There will be no study-specific approaches to transfusions or transfusion thresholds, and the decision to transfusion will be made as part of current clinical care by the treating clinicians. No study-specific blood draws will occur and all samples will be obtained from residual samples collected for clinical care that are to be discarded.

Oxygen levels in the digestive tract will be measured before, during and after each blood transfusion using a tissue oxygen monitor called Near Infrared Spectroscopy (NIRS). By using this technology, the researchers intend to better understand intestinal blood flow patterns. RBC function in RBC products transfused to infants will be compared between the infants who develop TR-NEC and matched control infants who do not develop TR-NEC. The researchers will explore the clinical implications of severe anemia when infants are 28 to 34 weeks of postmenstrual age, which is when infants are vulnerable to NEC.

Currently, there are no inexpensive, simple, patient/healthcare provider-operated hemoglobin tests available for diagnosing and assessing the degree of anemia without the use of a blood draw. To that end, Emory investigators have recently developed an algorithm that enables patients/healthcare providers to check if a patient is anemic by simply taking a picture of their fingernail beds on a Smartphone, and running the algorithm on a computer using MATLAB. These studies have shown that the degree of pallor in the fingernail beds, correlates with physiologic levels of hemoglobin in the blood and determines whether or not the patient is anemic. To date, the accuracy of this device has only been tested on adults and older children. Having an accurate and noninvasive means of testing for anemia in VPT infants would reduce the number of blood draws required, decrease the common side effects of phlebotomy, transfusion of RBCs, and would potentially be more cost-effective. As an additional study aim, the researchers of this study seek to develop a new image analysis algorithm (IAA) to predict hemoglobin level and anemia status from fingernail photos. The fingernail beds of VPT infants are extremely small and therefore it is uncertain if the nail bed is the most accurate site to assess anemia in these infants. To determine which site is most accurate in this population pictures will be taken of the fingernail beds, the toe nail beds, the palm of the hand and the sole of the foot with be photographed and analyzed.

Leftover samples of blood, urine, stool, and breast milk will be frozen, and stored and in the event a baby develops a digestive tract complication the samples will be studied in a laboratory to identify markers that indicate a healthy digestive tract versus illness. Immune cell function, digestive tract microbial changes, and serum cytokine levels will be compared between very preterm infants who develop NEC and those who do not.

• Study Type: Observational
• Enrollment (Actual): 324

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital - Neonatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 days (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Extremely low birth weight newborn infants born at Emory University Hospital Midtown, Grady Health System, and Northside Hospital Neonatology. Infants will be followed at Children's Healthcare of Atlanta.

Description

Inclusion Criteria:

• Birth weight ≤1250 grams
• Postnatal age within 7 days of birth

Exclusion Criteria:

• Infant not expected to live beyond 7 days of life based on assessment of treating neonatologist
• Severe congenital abnormality expected to affect life expectancy
• RBC or platelet transfusion at an outside institution occurring prior to screening
• Maternal refusal to participate

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ELBW Infants with Prolonged Irradiation Storage Time; Extremely Low Birth Weight Infants whose Red Blood Cell (RBC) transfusion had prolonged Irradiation Storage Time (IST) being tested with metabolomics profile.	Device: Near Infrared Spectroscopy; INVOS 5100C Cerebral/Somatic Oximeter is an FDA-approved device used to measure renal and mesenteric tissue oxygenation, as defined by regional oxygenation saturation levels (rSO2). Two probe site monitoring will be used to evaluate differential tissue bed oxygenation. Adhesive sensor probes are applied to the periumbilical area for mesenteric monitoring and to the flank area for renal monitoring.; Other Names: NIRS
ELBW Infants without Irradiation Storage; Extremely Low Birth Weight Infants whose Red Blood Cell (RBC) transfusion did not have Irradiation Storage being tested with metabolomics profile.	Device: Near Infrared Spectroscopy; INVOS 5100C Cerebral/Somatic Oximeter is an FDA-approved device used to measure renal and mesenteric tissue oxygenation, as defined by regional oxygenation saturation levels (rSO2). Two probe site monitoring will be used to evaluate differential tissue bed oxygenation. Adhesive sensor probes are applied to the periumbilical area for mesenteric monitoring and to the flank area for renal monitoring.; Other Names: NIRS
ELBW Infants Reaching the NEC Window; Extremely low birth weight infants who reach 28 to 34 postmenstrual week age, which is the NEC window.	Other: Non-invasive Image-based Anemia Assessment; A trained research associate will take 2 images (one with the camera flash on and one with the camera flash off) of the patient's fingernail beds, toe nail beds, palm of the hand and sole of the foot. Images will be taken within 24 hours, preceding, or following, each complete blood count (CBC) collection on each consented patient. The anemia diagnosing algorithm will then be run on the images.
ELBW Infants; Extremely low birth weight infants having intestinal microbial profiles examined via stool collected from discarded diapers, and immune cell function and serum cytokine levels examined using residual blood.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mesenteric Tissue Oxygenation	Mesenteric tissue oxygenation is measured in infants receiving RBC transfusion. Mesenteric regional saturation of oxygen (MES-rSO2) levels are measured via the INVOS 5100C Cerebral/Somatic Oximeter by applying an adhesive sensor probe to the patient's periumbilical area for mesenteric monitoring. MES-rSO2 will be compared between infants receiving RBC transfusion with and without IST.	60 Minutes prior to transfusion to 48 hours after transfusion
Infants Developing TR-NEC	Development of TR-NEC will be compared between infants receiving RBC transfusion with and without IST.	60 Minutes prior to transfusion to 48 hours after transfusion
Inhibition of NO-Mediated Vasodilation	Inhibition of NO-mediated vasodilation will be used to assess RBC function among transfused infants who develop TR-NEC and matched control infants who do not develop TR-NEC.	60 Minutes prior to transfusion to 48 hours after transfusion
Metabolic Changes of Red Blood Cells	Functional defects of transfused RBCs will be examined to assess metabolic changes of RBCs among transfused infants who develop TR-NEC and matched control infants who do not develop TR-NEC.	60 Minutes prior to transfusion to 48 hours after transfusion
Mesenteric Tissue Oxygenation During the NEC Window Period	ELBW infants that reach the window when NEC typically occurs will be further compared as those with vs without anemia. Regional Oxygenation Saturation Levels (rSO2) are measured via the INVOS 5100C Cerebral/Somatic Oximeter by applying an adhesive sensor probe to the patient's periumbilical area for mesenteric monitoring. NIRS will be performed once per week (whether transfused or not) for a 48 hour period starting each Monday (day of routine lab draw to evaluate anemia).	28 to 34 Weeks Post Menstrual Age
Immune Cell Function	Anemia significantly modulates immune function and may predispose infants to NEC through alterations in T cell activation and the presence of immunomodulatory erythroid precursors. Immune cell function profiles will be compared between infants who develop TR-NEC and matched controls who do not.	Up to 90 days of age
Microbial Changes	Alterations in the microbiota may further drive dysregulated immune function toward increased overall inflammation and the development of NEC. Microbial profiles will be compared between infants who develop TR-NEC and matched controls who do not.	Up to 90 days of age
Serum Cytokine Levels	Serum cytokine levels will be compared between infants who develop TR-NEC and matched controls who do not.	Up to 90 days of age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of a Clustering Method for Identification of Anemia	The researchers will develop a new clustering method for further understanding sub-population structures of fingernail photos and image megadata to identify subgroups of infants with high anemia risk.	Up to 90 days of age
Image Analysis Algorithm	The researchers will develop a new clustering method for further understanding sub-population structures of fingernail photos and image megadata to identify subgroups of infants with high anemia risk.	Up to 90 days of age
Image Analysis Algorithm (IAA)	The researchers will use an image analysis algorithm (IAA) to examine structural information in fingernail photos and image metadata to accurately predict hemoglobin level and anemia status.	Up to 90 days of age

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Ravi Patel, MD, MSc, Emory University

Publications and helpful links

General Publications

• Marin T, Patel RM, Roback JD, Stowell SR, Guo Y, Easley K, Warnock M, Skvarich J, Josephson CD. Does red blood cell irradiation and/or anemia trigger intestinal injury in premature infants with birth weight </= 1250 g? An observational birth cohort study. BMC Pediatr. 2018 Aug 11;18(1):270. doi: 10.1186/s12887-018-1241-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): February 19, 2026
• Study Completion (Actual): February 19, 2026

Study Registration Dates

• First Submitted: April 13, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimated): April 18, 2016

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Red Blood Cell Transfusion; Extremely Low Birth Weight; Digestive tract problems
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hematologic Diseases; Gastroenteritis; Enterocolitis; Hemic and Lymphatic Diseases; Anemia; Enterocolitis, Necrotizing; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Imaging; Chemistry Techniques, Analytical; Spectrum Analysis; Spectroscopy, Near-Infrared
• Other Study ID Numbers: IRB00083691; 2P01HL086773 (U.S. NIH Grant/Contract); 1R01HL138714 (U.S. NIH Grant/Contract); 2025P010798 (Other Identifier: Emory IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No