Premature Infants, Stool Bacterial Composition, Growth
Conditions
Keywords
Probiotic, Prebiotic, NEC, Premature infants, commensal flora
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTProBioPlus
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.
DIETARY_SUPPLEMENTCulturelle
Culturelle is advertised as containing Lactobacillus rhamnosus GG. The dose was 5 x 10e8 twice daily.
OTHERPlacebo
A dilute preparation of pregestimil powder formulated to have a similar appearance to the probiotic products
Sponsors
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 7 Days
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain | 5 weeks | Weight at five weeks minus birth weight |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool Colonization With Bifidobacteria | 4 weeks | 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. |
| Stool Short Chain Butyric Acid Content | 4 weeks | — |
Countries
United States
Participant flow
Recruitment details
Premature infants were enrolled from October 2004 to Aug 2006 at the University of California Davis Medical Center Neonatal Intensive Care Unit in Sacramento, California.
Participants by arm
| Arm | Count |
|---|---|
| ProBioPlus ProBioPlus (three bifidobacteria, Lactobacillus acidophilus, and fructo-oligosaccharide) at a dose of 5 x 10e8 organisms twice daily for five weeks | 31 |
| Culturelle Culturelle (Lactobacillus ramnosus GG plus fructo-oligosaccharide) at a dose of 5x10e8 organisms twice daily for five weeks. | 30 |
| Placebo A dilute preparation of pregestimil formula (negligible caloric content) | 29 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Removed at parents request | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Culturelle | Placebo | ProBioPlus | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 30 Participants | 29 Participants | 31 Participants | 90 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 29.5 weeks gestation STANDARD_DEVIATION 2.6 | 30.2 weeks gestation STANDARD_DEVIATION 2.4 | 29.3 weeks gestation STANDARD_DEVIATION 2.6 | 29.7 weeks gestation STANDARD_DEVIATION 2.5 |
| Region of Enrollment United States | 30 participants | 29 participants | 31 participants | 90 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 12 Participants | 31 Participants |
| Sex: Female, Male Male | 21 Participants | 19 Participants | 19 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 31 | 0 / 30 | 0 / 29 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 | 0 / 29 |
Outcome results
Primary
Weight Gain
Weight at five weeks minus birth weight
Time frame: 5 weeks
Population: Infants left the study as they were discharged from the NICU, therefore many of the infants were not available for measurement at five weeks. The number reported is the number of infants remaining in the study at 5 weeks. Weight in grams is reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ProBioPlus | Weight Gain | 618 Grams | Standard Deviation 201 |
| Culturelle | Weight Gain | 590 Grams | Standard Deviation 186 |
| Placebo | Weight Gain | 682 Grams | Standard Deviation 208 |
p-value: >0.5Mixed-effects regression
Secondary
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.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ProBioPlus | Stool Colonization With Bifidobacteria | 7 Participants |
| Culturelle | Stool Colonization With Bifidobacteria | 2 Participants |
| Placebo | Stool Colonization With Bifidobacteria | 3 Participants |
p-value: 0.06Chi-squared
Secondary
Stool Short Chain Butyric Acid Content
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ProBioPlus | Stool Short Chain Butyric Acid Content | 5.1 nmoles per mg stool | Standard Deviation 4.8 |
| Culturelle | Stool Short Chain Butyric Acid Content | 8.3 nmoles per mg stool | Standard Deviation 5.6 |
| Placebo | Stool Short Chain Butyric Acid Content | 7.7 nmoles per mg stool | Standard Deviation 5.5 |
p-value: >0.05ANOVA