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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01735578
First Posted: November 28, 2012
Last Update Posted: May 5, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Utah
  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 ]
    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.


Enrollment: 52
Study Start Date: October 2012
Study Completion Date: April 2015
Primary Completion Date: April 2015 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Weeks   (Child)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01735578


Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Mariana Baserga, MD University of Utah
  More Information

Publications:
Yost CC. Neonatal necrotizing enterocolitis: diagnosis, management, and pathogenesis. J Infus Nurs. 2005 Mar-Apr;28(2):130-4. Review.
Frost BL, Jilling T, Caplan MS. The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis. Semin Perinatol. 2008 Apr;32(2):100-6. doi: 10.1053/j.semperi.2008.01.001. Review.
Neu J, Mshvildadze M, Mai V. A roadmap for understanding and preventing necrotizing enterocolitis. Curr Gastroenterol Rep. 2008 Oct;10(5):450-7. Review.
Lemons JA, Bauer CR, Oh W, Korones SB, Papile LA, Stoll BJ, Verter J, Temprosa M, Wright LL, Ehrenkranz RA, Fanaroff AA, Stark A, Carlo W, Tyson JE, Donovan EF, Shankaran S, Stevenson DK. Very low birth weight outcomes of the National Institute of Child health and human development neonatal research network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics. 2001 Jan;107(1):E1.
Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res. 2008 Feb;63(2):117-23. Review.
Christensen RD, Lambert DK, Henry E, Wiedmeier SE, Snow GL, Baer VL, Gerday E, Ilstrup S, Pysher TJ. Is "transfusion-associated necrotizing enterocolitis" an authentic pathogenic entity? Transfusion. 2010 May;50(5):1106-12. doi: 10.1111/j.1537-2995.2009.02542.x. Epub 2009 Dec 29.
Mally P, Golombek SG, Mishra R, Nigam S, Mohandas K, Depalhma H, LaGamma EF. Association of necrotizing enterocolitis with elective packed red blood cell transfusions in stable, growing, premature neonates. Am J Perinatol. 2006 Nov;23(8):451-8. Epub 2006 Sep 28.
Josephson CD, Wesolowski A, Bao G, Sola-Visner MC, Dudell G, Castillejo MI, Shaz BH, Easley KA, Hillyer CD, Maheshwari A. Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants? J Pediatr. 2010 Dec;157(6):972-978.e1-3. doi: 10.1016/j.jpeds.2010.05.054. Epub 2010 Jul 21.
Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma EF. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cell transfusion. J Pediatr. 2011 Mar;158(3):403-9. doi: 10.1016/j.jpeds.2010.09.015. Epub 2010 Nov 10.
Singh R, Visintainer PF, Frantz ID 3rd, Shah BL, Meyer KM, Favila SA, Thomas MS, Kent DM. Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants. J Perinatol. 2011 Mar;31(3):176-82. doi: 10.1038/jp.2010.145. Epub 2011 Jan 27.
El-Dib M, Narang S, Lee E, Massaro AN, Aly H. Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants. J Perinatol. 2011 Mar;31(3):183-7. doi: 10.1038/jp.2010.157. Epub 2011 Jan 20.
Baserga MC, Gregory GA, Sola A. Cerebrovascular response in small preterm infants during routine nursery gavage feedings. Biol Neonate. 2003;83(1):12-8.
Dave V, Brion LP, Campbell DE, Scheiner M, Raab C, Nafday SM. Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding. J Perinatol. 2009 Mar;29(3):213-8. doi: 10.1038/jp.2008.189. Epub 2008 Nov 20.
Dani C, Pratesi S, Fontanelli G, Barp J, Bertini G. Blood transfusions increase cerebral, splanchnic, and renal oxygenation in anemic preterm infants. Transfusion. 2010 Jun;50(6):1220-6. doi: 10.1111/j.1537-2995.2009.02575.x. Epub 2010 Jan 22.
Gay AN, Lazar DA, Stoll B, Naik-Mathuria B, Mushin OP, Rodriguez MA, Burrin DG, Olutoye OO. Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets. J Pediatr Surg. 2011 Jun;46(6):1034-40. doi: 10.1016/j.jpedsurg.2011.03.025.
Fortune PM, Wagstaff M, Petros AJ. Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may be able to predict splanchnic ischaemia in neonates. Intensive Care Med. 2001 Aug;27(8):1401-7.

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01735578     History of Changes
Other Study ID Numbers: 58673
First Submitted: November 22, 2012
First Posted: November 28, 2012
Last Update Posted: May 5, 2015
Last Verified: December 2014

Keywords provided by University of Utah:
splanchnic oxygen saturations

Additional relevant MeSH terms:
Enterocolitis
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases


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