Intestinal Permeability in Preterm Infants (IPPI)

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.

Measurement of intestinal permeability by use of mon- digestible sugars known not to cross the intestinal barrier in normal healthy intestinal tissue

Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio)

Inclusion Criteria: <5 days Gestational age 24-32 weeks Exclusion criteria: Nonviable or planned withdrawal of care Significant GI dysfunction (e.g. heme-positive stools, abdominal distension (girth >2 cm baseline), or bilious emesis/aspirates. Triplet or higher order multiple Severe asphyxia Lethal chromosome abnormalities Cyanotic congenital heart disease Intestinal atresia or perforation Abdominal wall defects Known galactosemia or other galactose intolerance

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