Effects of Probiotic and Prebiotic Combinations on Premature Infants

Study Overview
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Brief Summary
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The purpose of this study is to see how oral preparations containing both probiotics and prebiotics impact the growth, bacterial colonization of the intestines, and fecal short chain fatty acid content in premature infants. Our hypothesis is that short term growth will be improved, the stool will have more healthy bacteria, and the fecal short chain fatty acid content will increase in the babies who receive the probiotic/prebiotic combinations compared to control groups.

Detailed Description
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Premature infants are at risk for a devastating infection of the intestines due to the immaturity of their intestines and immune system. Probiotics are bacteria with healthful qualities that are taken by mouth to improve the number of healthy bacteria in the intestines. Probiotics have been shown in several studies outside the U.S. to decrease the risk of serious intestinal infection and in one small study to improve the rate of weight gain in premature infants. Prebiotics are food supplements that stimulate the growth of healthy bacteria and suppress the growth of unhealthy bacteria. Prebiotics have been shown to improve the numbers of healthy bacteria in the stool of premature babies. Our study is designed to compare two over the counter probiotic/prebiotic combinations to each other and to a control group. Infants less than 35 weeks with a birthweight of 750-2000 gm are eligible and must be enrolled in the study within the first week of life. The babies are randomly assigned to either a control group (no probiotic/prebiotic, just a placebo), a group which receives Culturelle (Lactobacillus rhamnosus GG plus fructo-oligosaccharide, ConAgra), or a group which receives ProBioPlus (three strains of Bifidobacteria plus Lactobacillus acidophilus plus fructo-oligosaccharide, UAS Laboratories). The babies receive the study product by mouth twice daily for 28 days or until discharge (whichever comes first). Weekly measurements (weight, length, head size) and stool cultures are performed. Clinical progress is closely monitored and any episodes of infection are recorded.

Official Title
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Efficacy of a Prebiotic and Probiotic Combination in Preterm Infants

Conditions
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Premature Infants, Stool Bacterial Composition, Growth

Intervention / Treatment
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* Dietary Supplement: ProBioPlus
* Dietary Supplement: Culturelle
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: less than 35 weeks gestation, birth weight 750-2000 grams born in or transferred to University of California Davis Medical Center within first week of life less than eight days of age at the time of enrollment Exclusion Criteria: Severe intestinal or cardiac congenital anomalies

Ages Eligible for Study
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Maximum Age: 7 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ProBioPlus<br> | Dietary Supplement: ProBioPlus<br>* ProBioPlus is advertised as containing Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium infantis, and Bifidobacterium bifidum plus inulin. The dose given was 5 x 10e8 twice daily.<br>|
| Active Comparator: Culturelle<br> | Dietary Supplement: Culturelle<br>* Culturelle is advertised as containing Lactobacillus rhamnosus GG. The dose was 5 x 10e8 twice daily.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* A dilute preparation of pregestimil powder formulated to have a similar appearance to the probiotic products<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Gain | Weight at five weeks minus birth weight | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool Colonization With Bifidobacteria | Using standard culture techniques, we measured how many of the first 11 infants in each arm of the study grew bifidobacteria in their feces after four weeks of treatment. | 4 weeks | 
| Stool Short Chain Butyric Acid Content |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotic, Prebiotic, NEC, Premature infants, commensal flora