Intestinal Permeability in Preterm Infants

Study Overview
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Brief Summary
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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.

Detailed Description
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The proposed study will evaluate the intestinal permeability measured by the urinary La/Rh ratio at one timepoint between d7-10 of life in 200 preterm infants 24-32 weeks gestation in preparation for a future study of probiotics to improve intestinal permeability in this population. Primary Objective: To estimate mean and variance in IP measured by urinary Lactulose/Rhamnose ratio at 7-10d of life in neonates born between 24 and 32 weeks of gestational age. Secondary Objectives 1) To assess stool microbiome characteristics in association with intestinal permeability in preterm infants measured by the urinary lactulose/rhamnose ratio.

Official Title
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Gut Permeability in Very Low Birth Weight Infants

Conditions
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Prematurity, Intestinal Permeability

Intervention / Treatment
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* Drug: Lactulose -rhamnose solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 4 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Lactulose - rhamnose solution<br>Preterm Infants age 24-32 weeks gestation | Drug: Lactulose -rhamnose solution<br>* Measurement of intestinal permeability by use of mon- digestible sugars known not to cross the intestinal barrier in normal healthy intestinal tissue<br>* Other names: dual sugar solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal Permeability | Intestinal Permeability measured by urinary excretion of orally administered lactulose/rhamnose (La/Rh ratio) | 7-10 days postnatal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool Alpha-1 Antitrypsin | Stool alpha-1 antitrypsin concentrations | 7-10 days postnatal | 
| Stool Microbiota Relative Abundance | Relative abundance (%) Clostridiales species | 7-10 days postnatal | 
| Breastmilk Feeding Duration Prior to La/Rh Measurement | Number of days breast milk feeding prior to La/Rh measurement between d7-10 days of age. | 7-10 days postnatal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intestinal permeability, preterm infants, dual sugar test, intestinal microbiota