Effects of Probiotic and Prebiotic Combinations on Premature Infants

Efficacy of a Prebiotic and Probiotic Combination in Preterm Infants

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.

Study Overview

• Status: Completed
• Conditions: Growth; Premature Infants; Stool Bacterial Composition
• Intervention / Treatment: Dietary supplement: ProBioPlus; Dietary supplement: Culturelle; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Other: Placebo; A dilute preparation of pregestimil powder formulated to have a similar appearance to the probiotic products
ACTIVE_COMPARATOR: ProBioPlus	Dietary supplement: ProBioPlus; 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.
ACTIVE_COMPARATOR: Culturelle	Dietary supplement: Culturelle; Culturelle is advertised as containing Lactobacillus rhamnosus GG. The dose was 5 x 10e8 twice daily.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Michael P Sherman, MD, University of California, Davis

Publications and helpful links

General Publications

• Underwood MA, Salzman NH, Bennett SH, Barman M, Mills DA, Marcobal A, Tancredi DJ, Bevins CL, Sherman MP. A randomized placebo-controlled comparison of 2 prebiotic/probiotic combinations in preterm infants: impact on weight gain, intestinal microbiota, and fecal short-chain fatty acids. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):216-25. doi: 10.1097/MPG.0b013e31818de195.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (ACTUAL): August 1, 2006
• Study Completion (ACTUAL): August 1, 2007

Study Registration Dates

• First Submitted: January 23, 2006
• First Submitted That Met QC Criteria: January 23, 2006
• First Posted (ESTIMATE): January 25, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): January 28, 2010
• Last Update Submitted That Met QC Criteria: December 31, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Prebiotic; Premature infants; Probiotic; NEC; commensal flora
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 2004122333-1