Necrotizing enterocolitis (NEC) is a life-threatening, gastrointestinal emergency
characterized by increased intestinal permeability, affects approximately 7 to 10% of infants
<1500 g birthweight, and typically occurs within 7 to 14 days of birth. Mortality is as high
as 30-50%. Prematurity is the greatest risk factor for the development of NEC due to the
physiological immaturity of the gastrointestinal tract and altered or abnormal gut
microbiota. Several studies have demonstrated that the initiation of an intense systemic and
local inflammatory cascade leads to intestinal necrosis. The human intestine is lined by a
single layer of cells exquisitely responsive to multiple stimuli and is populated by a
complex climax community of microbial partners. Under normal circumstances, these intestinal
cells form a tight but selective barrier to "friends and foes": microbes and most
environmental substances are held at bay, but nutrients are absorbed efficiently. Epithelial
barrier integrity is itself dynamic and matures over time starting soon after birth, though
the mechanisms regulating dynamic permeability are poorly understood. Low birth weight,
prematurity, and early postnatal age are associated with a leaky gut. Although intestinal
permeability is higher at birth in preterm than term infants, there is usually rapid
maturation of the intestinal barrier over the first few days of life in both populations. The
investigators hypothesize that increased levels of measures of intestinal permeability (serum
zonulin, urine lactulose/rhamnose (LA/Rh), and fecal alpha1- antitrypsin will identify
infants at high risk for NEC. The purpose of the study is to determine whether measurement of
intestinal permeability in serum will correlate with other markers of intestinal barrier
leakiness measured in urine (LA/Rh) and stool (alpha-1 antitrypsin. If there is good
correlation, then zonulin or serum rhamnose may be a useful measure to identify preterm
babies at risk for NEC.
Phase:
Phase 1
Details
Lead Sponsor:
University of Maryland University of Maryland, Baltimore
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)