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| ID | Type | Description | Link |
|---|---|---|---|
| R01HD093826 | U.S. NIH Grant/Contract | View source |
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Lack of enrollment
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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The purpose of this study is to characterize the time to maturation of neutrophil extracellular trap(NET) formation capability in polymorphonuclear leukocytes(PMNs) isolated from newborn premature and term infants. Preterm infants who are enrolled into the study who then go on to require surgery <1 year due to surgical NEC, will have the NET formation reassessed. This study will also determine whether NETs contribute to the pathogenesis of necrotizing enterocolitis (NEC). We hypothesize that NET formation contributes to the pathogenesis of NEC by inappropriately releasing degradative proteins and tissue destructive enzymes into the inflammatory milieu of the premature infant gastrointestinal tract following bacterial translocation. We also hypothesize that the delay in NEC development in premature infants (3rd - 4th week of life) as compared to at-risk term infants (1st week of life) results from a developmental delay in PMN ability to form NETs.
Prematurely born infants are at risk for necrotizing enterocolitis (NEC), the most common gastrointestinal emergency encountered in the newborn intensive care unit. This disease occurs in between 5 - 10% of infants born at less than 30 weeks gestation or less than 1500 grams birth weight. In these patients, NEC routinely develops during the 3rd or 4th week of life. NEC rarely occurs in infants born closer to term; for these patients NEC usually develops during the 1st week of life. So far, no one has explained the inverse relationship between gestational age at birth and the delay in NEC development.
Recently, our laboratory described for the first time an inherent deficiency of innate immunity in newborn infants - failure of neutrophil extracellular trap formation. Neutrophil extracellular traps or NETs are complex lattices of extracellular chromatin and DNA decorated with anti-microbial proteins and degradative enzymes which trap and kill microbes. When the neutrophils of newborn infants develop the ability to form NETs and whether the maturation of NET formation correlates with development of NEC in at risk infants remains unknown.
We have therefore undertaken the following study best described as a prospective, in vitro longitudinal cellular biology study of LPS/PAF-stimulated PMNs isolated from the cord and peripheral blood of premature infants at risk for NEC and from term infants not considered at risk for NEC. We will also assay for NET formation in gastrointestinal tissue samples obtained at the time of surgery for severe NEC in enrolled prematurely born infants. These studies are the first of their kind and aim to answer these important questions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prematurely born infants in the NICU | Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤1500 grams or <30 weeks gestational age at birth. | ||
| Healthy term infants | Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery | ||
| Subset: Enrolled preterm infants having surgery at <1 year old for NEC | Enrolled preterm infants who require surgery for NEC within their first year of life for |
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| Measure | Description | Time Frame |
|---|---|---|
| Time to Maturation of Neutrophil Extracellular Trap(NET) Formation | The objective is to characterize the time to maturation of NET formation capability in polymorphonuclear leukocytes(PMNs)isolated from newborn infants. | 60 days |
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Inclusion Criteria:
Exclusion Criteria:
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Preterm and healthy term infants born at the University of Utah Hospital. A subset of preterm infants needing surgery <1 year of age, will be reassessed.
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| Name | Affiliation | Role |
|---|---|---|
| Christian C Yost, MD | University of Utah | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84108 | United States | ||
| Primary Children's Medical Center |
No infants required surgery during the first year of life, therefore no participants were evaluated in the surgical cohort
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| ID | Title | Description |
|---|---|---|
| FG000 | Prematurely Born Infants in the NICU | Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤1500 grams or <30 weeks gestational age at birth |
| FG001 | Healthy Term Infants | Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery |
| FG002 | Infants Having Surgery at <1 Year Old | Infants who require surgery within their first year of life for NEC |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
None of our recruited prematurely born infants in the NICU required surgery in the first year of life.
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| ID | Title | Description |
|---|---|---|
| BG000 | Prematurely Born Infants in the NICU | Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤1500 grams or <30 weeks gestational age at birth |
| BG001 | Healthy Term Infants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Maturation of Neutrophil Extracellular Trap(NET) Formation | The objective is to characterize the time to maturation of NET formation capability in polymorphonuclear leukocytes(PMNs)isolated from newborn infants. | No study participants required surgery during the first year of life. | Posted | Mean | Full Range | Days | 60 days |
|
First 2 months of life.
Not a clinical study. NEC was a complication of prematurity, not a complication of our observational study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prematurely Born Infants in the NICU | Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤1500 grams or <30 weeks gestational age at birth |
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This is an observational study designed to evaluate NEC incidence with in vitro assessment of neutrophil neutrophil extracellular trap formation. There are too few study participants to draw any meaningful correlations between in vitro NET formation by participant neutrophils and the incidence of NEC in this at-risk population.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christian Con Yost, MD | University of Utah - Pediatrics | 801-518-7052 | christian.yost@u2m2.utah.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2019 | Jun 1, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D047928 | Premature Birth |
| D020345 | Enterocolitis, Necrotizing |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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Blood and intestinal tissue samples
| Salt Lake City |
| Utah |
| 84112 |
| United States |
Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery
| BG002 | Subset: Enrolled Preterm Infants Having Surgery at <1 Year Old | Enrolled preterm infants who require surgery within their first year of life |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | Day |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Infants Having Surgery at <1 Year Old | Infants admitted to the PCMC same-day surgery unit in preparation for elective surgery within the first year of life |
|
|
| 1 |
| 11 |
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Healthy Term Infants | Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery | 0 | 3 | 0 | 3 | 0 | 3 |
| EG002 | Infants Having Surgery at <1 Year Old | Infants who go on to have surgery at <1 year of age will have NET formation reassessed. No enrolled infants required surgery at < 1 year of age | 0 | 0 | 0 | 0 | 0 | 0 |
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| D000091642 | Urogenital Diseases |
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |