Transfusion-related Inflammatory Cytokine and Neutrophil Extracellular Trap Quantification in Neonates

May 1, 2015 updated by: University of Utah

Transfusion-related Inflammatory Cytokine and Neutrophil Extracellular Trap Quantification in Neonates.

Despite many advances in neonatal care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality among premature infants. NEC is the most common life-threatening gastrointestinal emergency encountered in the neonatal intensive care unit, affecting between 3.8% and 13% of very low birthweight (VLBW) infants (1-3). More recently interest has intensified regarding the possible association between "elective" red blood cell (RBC) transfusions in premature infants and the subsequent development of NEC (4-9). On a physiological basis, a few 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]; and 2) increased splanchnic blood flow following RBC transfusion leading to reperfusion injury of gut mucosa.

Aim 1. This study will quantify inflammatory cytokine profiles in anemic infants cared for in the NICU prior to and after transfusion with packed red blood cells (PRBC), as dictated by current clinical guidelines for treatment of anemia, and prospectively assess for clinical signs and symptoms of NEC following each transfusion event.

Aim 2. Polymorphonuclear leukocytes (PMNs) isolated from the pre- and post-transfusion blood samples will be assessed in vitro for neutrophil extracellular traps (NET) formation.

Aim 3. A) To determine whether significant anemia preceding a RBC transfusion is associated with impaired intestinal oxygenation, and whether a RBC transfusion temporarily increases splanchnic oxygenation. We postulate that the CSOR will be low (<0.75) at baseline measurement in infants with hemodynamically significant anemia, and that RBC transfusion will temporarily increase intestinal perfusion in that particular group of babies.

B) To determine whether alterations in mesenteric regional oxygenation saturation(rSO2) can predict the development of NEC in VLBW infants. We hypothesize that overall cerebro-splanchnic oxygenation ratio (CSOR) values will be significantly lower among very low birth weight (VLBW) infants that develop NEC, when compared to CSOR values obtained in infants that do not develop NEC following RBC transfusion.

Study Overview

Status

Terminated

Conditions

Study Type

Observational

Enrollment (Actual)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Salt Lake City, Utah, United States, 84112
        • Primary Children's Medical Center
      • Salt Lake City, Utah, United States, 84108
        • University of Utah Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 2 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Premature infants admitted into the University of Utah (UUMC), Primary Children's Medical Center (PCMC) and Intermountain Medical Center's (IMC) Neonatal Intesive Care Unit (NICUs)

Description

Inclusion Criteria:

  • Inpatient in NICU at UUMC, PCMC, or IMC
  • Gestational age at birth ≤ 32 weeks
  • Birth weight ≤ 1500 grams
  • Age ≤ 12 weeks of life

Exclusion Criteria:

  • Lack of parental consent
  • Multiple congenital anomalies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Infants requiring PRBCs
Premature infants who require PRBCs for anemia that is not related to sepsis, surgery, NEC or immunologic abnormalities.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum cytokine content
Time Frame: 6 hrs
Plasma samples will be analyzed for the protein content of 13 different cytokines via a multiplexed sandwich capture assay performed at the ARUP Institute for Experimental and Clinical Pathology. The cytokines and chemokines assayed will include: CD40 ligand, interferon-gamma, interleukin-10, interleukin-12, interleukin-13, interleukin-1-β, interleukin-2, interleukin-2-receptor, interleukin-4, interleukin-5, interleukin-6, IL-8, and Tumor Necrosis Factor-alpha. In addition, we will assay components of the complement pathway including: total hemolytic complement, C3a, C5a, and FAB fragments in the alternative complement pathway. Cytokine protein levels before and after transfusion will be compared to each other and to the PRBC sample cytokine content.
6 hrs

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of NET formation
Time Frame: 6 hrs
PMNs will be isolated from the participant blood samples following removal of the plasma via positive immunoselection. They will then be stimulated in vitro with NET-inducing stimuli such as lipopolysaccharide or platelet-activating factor for 1 hour under standard conditions and assayed for NET formation both qualitatively via confocal microscopy and quantitatively via histone H3 supernatant content as determined by ELISA and/or western blotting.
6 hrs

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tissue oxygenation indexes (TOI) of cerebral (TOI brain ) and splanchnic (TOIabdo) regions
Time Frame: 53 hrs
Tissue oxygenation indexes (TOI) of cerebral (TOI brain ) and splanchnic (TOIabdo) regions will be measured using NIRS and the values reported as CSOR (TOIabdo/TOI brain). Measurements will be continuously recorded and data points obtained for 30 minute periods at baseline or T0 (prior to PRBC transfusion), and every hour during the RBC transfusion (T1, T2, T3 and T4)
53 hrs
Mesenteric rSO2
Time Frame: 53 hrs

To determine whether alterations in mesenteric rSO2 can predict the development of NEC in VLBW infants.

For this aim, TOI and CSOR will be measured every 3 hours for 30 minute periods in the first 48 hours following RBC transfusion (T5 to T16)(Table 1). By obtaining measurements during this time frame, we intend to capture the period of greatest susceptibility to develop NEC in this population.
53 hrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Investigators

  • Principal Investigator: Susan Wiedmeier, MD, University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

November 22, 2012

First Submitted That Met QC Criteria

November 22, 2012

First Posted (Estimate)

November 28, 2012

Study Record Updates

Last Update Posted (Estimate)

May 5, 2015

Last Update Submitted That Met QC Criteria

May 1, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 51050

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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