Necrotizing Enterocolitis, Prematurity
Conditions
Keywords
premature infants, polymorphonuclear leukocytes, PMNs, neutrophil extracellular traps, NET formation, necrotizing enterocolitis
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Utah
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
Yes
Inclusion criteria
1. Preterm infant patients delivered at UUMC and hospitalized in the NICU who are ≤ 1500 grams or \<30 weeks gestational age at birth 2. Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery
Exclusion criteria
* No other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maturation of Neutrophil Extracellular Trap(NET) Formation | 60 days | The objective is to characterize the time to maturation of NET formation capability in polymorphonuclear leukocytes(PMNs)isolated from newborn infants. |
Countries
United States
Participant flow
Pre-assignment details
No infants required surgery during the first year of life, therefore no participants were evaluated in the surgical cohort
Participants by arm
| Arm | Count |
|---|---|
| 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 | 11 |
| Healthy Term Infants Term infants delivered at UUMC without complication, either via cesarean section or vaginal delivery | 3 |
| Subset: Enrolled Preterm Infants Having Surgery at <1 Year Old Enrolled preterm infants who require surgery within their first year of life | 0 |
| Total | 14 |
Baseline characteristics
| Characteristic | Prematurely Born Infants in the NICU | Healthy Term Infants | Subset: Enrolled Preterm Infants Having Surgery at <1 Year Old | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 11 Participants | 3 Participants | 0 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 1 Day | 1 Day | — | 1 Day |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | — | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 3 Participants | — | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 3 Participants | — | 14 Participants |
| Region of Enrollment United States | 11 participants | 3 participants | — | 14 participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | — | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | — | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 11 | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 0 / 11 | 0 / 3 | 0 / 0 |
| serious Total, serious adverse events | 0 / 11 | 0 / 3 | 0 / 0 |
Outcome results
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.
Time frame: 60 days
Population: No study participants required surgery during the first year of life.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Prematurely Born Infants in the NICU | Time to Maturation of Neutrophil Extracellular Trap(NET) Formation | 14 Days |
| Healthy Term Infants | Time to Maturation of Neutrophil Extracellular Trap(NET) Formation | 5 Days |