Splanchnic Tissue Oxygenation During Enteral Feedings in Anemic Premature Infants at Risk for Necrotizing Enterocolitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Utah
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01735578
First received: November 22, 2012
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency encountered in the newborn intensive care unit and represents a significant cause of morbidity and mortality in infants born prematurely. Among possible risk factors, a strong association between elective RBC transfusions in premature infants with anemia and the subsequent development of NEC has been consistently observed (6-11). However, a significant (and increasing) number of VLBW infants with anemia are managed with erythropoiesis stimulating agents (such as Epo) and iron and do not receive RBC transfusions during their hospital stay. The present study proposes to study this particular group of VLBW infants that remain with low (<28 %) hematocrit while receiving full enteral feedings.

The investigators hypothesize that significant anemia in VLBW infants will be associated with a baseline low cerebro-splanchnic oxygenation ratio (CSOR) (<0.75) as measured by NIRS, and that nasogastric feedings (NGF) in those particular patients will lead to further decreased splanchnic oxygenation. The investigators further postulate that CSOR values will be significantly lower among VLBW that develop NEC as compared to infants that do not.


Condition
Anemia of Prematurity
Necrotizing Enterocolitis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Splanchnic Tissue Oxygenation During Enteral Feedings in Anemic Premature Infants at Risk for Necrotizing Enterocolitis

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • cerebro-splanchnic oxygenation ratio (CSOR) measurements [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Stable premature infants who are being fed but have hematocrits lower than or equal to 28 will be continuously monitored using near-infrared spectroscopy (NIRS) in the cerebral and mesenteric regions for 24 hours.


Estimated Enrollment: 100
Study Start Date: October 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Premature infants with anemia
Inpatient premature infants at the University of Utah Neonatal Intensive Care Unit (NICU) with Hct < or = to 28 who are being fed and are stable.

Detailed Description:

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency encountered in the newborn intensive care unit and represents a significant cause of morbidity and mortality in infants born prematurely. This disease complicates the management of approximately 6 - 10% of very low birthweight (VLBW) infants and can result in significant feeding intolerance, intestinal perforation and/or death despite aggressive treatment (1). The sequence of events leading to NEC appears to be multifactorial and complex (2,3). While epidemiologic studies have identified multiple factors that appear to increase an infant's risk for the development of NEC, other than prematurity, no single predictive risk factor has been clearly delineated (4,5).

Among possible risk factors, a strong association between elective RBC transfusions in premature infants with anemia and the subsequent development of NEC has been consistently observed (6-11). Possible explanations for transfusion-associated NEC have been proposed: 1) the physiological impact of anemia that can initiate a cascade of events leading to ischemic-hypoxemic mucosal gut injury predisposing to NEC (10); 2) increased splanchnic blood flow following RBC transfusion leading to reperfusion injury of gut mucosa.

A significant (and increasing) number of VLBW infants with anemia are managed with erythropoiesis stimulating agents (such as Epo) and iron and do not receive RBC transfusions during their hospital stay. The present study proposes to study this particular group of VLBW infants that remain with low (<28 %) hematocrit while receiving full enteral feedings.

Near Infrared Spectroscopy (NIRS) is a non-invasive, FDA approved, bedside technology that allows determination of regional oxygen saturations (rSO2) in tissues such as the gut mesentery. Using NIRS, the oxygenation status of hemoglobin in tissues located 2-4 cm below the skin can be determined and recorded continuously (12). For instance, Dave et al. used NIRS to demonstrate that splanchnic rSO2, but not cerebral rSO2, increases after feeds in the stable prematurely born infant tolerating full bolus orogastric feedings (13). Of importance, the average hematocrit in this study group was 37% (±7) and therefore these babies had no significant anemia.

While no normative values exist for mesenteric rSO2 in premature infants, recent studies have explored NIRS use in determining gut hypoxia and ischemia (14). Abdominal NIRS was used to detect alterations of intestinal rSO2 and perfusion in premature piglets that developed NEC (15). In a prospective cohort study of 40 neonates with medical or surgical acute intraabdominal pathology, a cerebro-splanchnic oxygenation ratio (CSOR) of less than 0.75 predicted gut ischemia with 90% sensitivity (16).

While these studies support a role for NIRS monitoring of mesenteric rSO2, it is not clear whether 1) VLBW with significant anemia have perturbations in intestinal oxygenation and perfusion, and 2) alterations in mesenteric rSO2 predict the development of NEC in VLBW infants.

We hypothesize that significant anemia in VLBW infants will be associated with a baseline low CSOR (<0.75) as measured by NIRS, and that nasogastric feedings (NGF) in those particular patients will lead to further decreased splanchnic oxygenation. We further postulate that CSOR values will be significantly lower among VLBW that develop NEC as compared to infants that do not.

  Eligibility

Ages Eligible for Study:   up to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Premature infants admitted to the University of Utah NICU with significant anemia.

Criteria

Inclusion Criteria:

  1. Premature infants of ≤ 32 weeks gestational age
  2. anemia (hematocrit of ≤ 28 %)
  3. full enteral feedings
  4. stable clinical condition (no mechanical ventilation, no vasopressors, no sepsis)
  5. Age ≤ 12 weeks of life

Exclusion Criteria:

  1. Lack of parental consent
  2. Multiple congenital anomalies
  3. unstable clinical condition (mechanical ventilation, vasopressors, sepsis)
  4. Previous medical or surgical NEC (defined as ≥ Bell's Stage II disease)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735578

Contacts
Contact: Carrie Rau, RN 801-213-3360 carrie.rau@hsc.utah.edu

Locations
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Carrie Rau, RN    801-213-3360    carrie.rau@hsc.utah.edu   
Principal Investigator: Mariana Baserga, MD         
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Mariana Baserga, MD University of Utah
  More Information

Publications:
Josephson, C. D. et al. Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants? J Pediatr 157, 972-978 e971-973.
Blau, J. et al. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr 158, 403-409.

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01735578     History of Changes
Other Study ID Numbers: 58673
Study First Received: November 22, 2012
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
splanchnic oxygen saturations

Additional relevant MeSH terms:
Enterocolitis, Necrotizing
Enterocolitis
Anemia, Neonatal
Infant, Premature, Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Anemia
Hematologic Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 30, 2014