Intestinal Permeability in Preterm Infants
Condition: Prematurity; Intestinal Permeability
MeSH terms: Premature Birth
Intervention: Lactulose -rhamnose solution
Intervention description: Measurement of intestinal permeability by use of mon- digestible sugars known not to cross the intestinal barrier in normal healthy intestinal tissue
Intervention MeSH terms: Lactulose; Pharmaceutical Solutions
Phase: Phase 1
Study type: Interventional
Primary purpose: Screening
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 211.0
Sex: All
Maximum age: 4 Days
Healthy volunteers: No
Keywords: intestinal permeability; preterm infants; dual sugar test; intestinal microbiota

Summary:

      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 (urine
      lactulose/rhamnose (LA/Rh), and fecal alpha1- antitrypsin will identify infants at high risk
      for NEC and that intestinal probiotic strains will be associated with intestinal barrier
      maturation. The purpose of the study is to determine whether clinical factors in combination
      with non-invasive stool test such as antitrypsin (A1AT) and microbiota composition profile
      are associated with intestinal permeability determined by excretion of non-metabolized sugar
      probes in urine (LA/Rh ratio). These studies may lead to a non-invasive screening test to
      identify preterm infants at risk for NEC.
    

Eligibility criteria:

        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