Neutrophil Extracellular Trap Formation in Newborn Infants at Risk for Necrotizing Enterocolitis

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.

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

3. Infants admitted to the PCMC same-day surgery unit in preparation for elective surgery
within the first year of life.

Exclusion Criteria:

- No other exclusion criteria