The Effects of Probiotic Supplementation on Extremely Low Birthweight Infants

Study Overview
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Brief Summary
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This is a research study that will look at the effects of giving two nutritional supplements on extremely low birth infants (infants weighing less than 1000 grams or weighing less than approximately 2 lbs 3 1/2 ounces at birth). The nutritional supplements that will be studied are Culturelle for Kids/Culturelle Kids and Align. They are nutritional supplements that each contain a different probiotic. In this study the investigators will mainly be looking at the effect that these supplements may have on how well babies tolerate their feedings and how long they require supplemental intravenous fluids for nutritional support. The investigators will also, however, look at many other factors such as rate of growth, rates of infection, survival rate and the length of time the infant needs to be in the hospital. The investigators will also look at its effect on conditions/complications of prematurity such as bronchopulmonary dysplasia and chronic lung disease (chronic diseases of the lung associated with prematurity), necrotizing enterocolitis and intestinal perforations (serious diseases of the infant's intestines), retinopathy of prematurity (eye disease associated with prematurity), intracranial hemorrhage (bleeding into the brain) and patent ductus arteriosus (a blood vessel connecting two main blood vessels coming out of the heart that does not close spontaneously (by itself).

Detailed Description
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The purpose of this research study is to investigate the effect of the administration of the nutritional supplements, Culturelle for Kids/Kids Culturelle in combination with Align, containing the Probiotics Lactobacillus GG and Bifidobacterium Infantis, on feeding tolerance (as determined by the number of days infant is without enteral feedings due to feeding intolerance, number of days infant requires supplemental hyperalimentation/intravenous fluids for nutritional support and number of days to achieve full enteral feedings) in high risk extremely low birth weight infants.

Official Title
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The Effects of Probiotic Supplementation on Extremely Low Birthweight Infants

Conditions
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Feeding Tolerance

Intervention / Treatment
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* Dietary Supplement: Probiotic Supplemented Group
* Dietary Supplement: Control Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birthweight between 500-999 grams Apgar score greater than or equal to 3 at 5 minutes Infant free from any known major congenital anomalies or chromosomal/genetic anomalies Infant without any known cyanotic or complex congenital heart disease Infant NPO or on trophic enteral feedings than have been started less than 24 hours previously Infant without prior history of necrotizing enterocolitis or gastrointestinal perforation Infant without previous exposure to probiotics Infant that will be ready to start trophic feedings within the first 14 days of life Infant less than or equal to 14 days of age Infant born to HIV negative mother Written informed consent obtained from mother Exclusion Criteria: Infant born to HIV positive mother Infant with history of prior probiotic exposure Infant greater than 14 days of age Infant on enteral feedings for greater than 24 hours Infant with major congenital anomaly/chromosomal or genetic anomaly Infant with cyanotic/complex congenital heart disease Infant with previous gastrointestinal perforation/necrotizing enterocolitis 5 minute Apgar score < 3

Ages Eligible for Study
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Maximum Age: 14 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Supplemented Group<br>500,000,0000 cells of Lactobacillus GG (utilizing either Culturelle for Kids or Kids Culturelle preparation) and 500,000,000 cells of Bifidobacterium Infantis (utilizing Align capsule) diluted in 3 ml breastmilk/formula and administered enterally from first day of enteral feeds until term gestation/discharge/transfer/death (whichever occurs first) every day infant is receives enteral feedings | Dietary Supplement: Probiotic Supplemented Group<br> <br> * Other names: Bifidobacter Infantis;|
| Sham Comparator: Control Group<br>3 ml enteral feeding of breastmilk/formula administered once daily in addition to regularly prescribed enteral feedings from day of first feeding until term gestation/discharge/transfer/death (which ever occurs first) and administered every day that infant receives enteral feedings | Dietary Supplement: Control Group<br> <br> * Other names: Formula;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feeding Tolerance | Feeding Tolerance as determined by the number of days infant is without enteral feedings due to feeding intolerance, number of days infant requires supplemental hyperalimentation/intravenous fluids for nutritional support and number of days to achieve full enteral feedings | Evaluated on a daily basis until hospital discharge/transfer/death up until one year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necrotizing Enterocolitis (Bell's Stage 2 or greater) |  | Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until 1 year of age | 
| Culture proven sepsis without Necrotizing Enterocolitis |  | Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age | 
| Chronic Lung Disease |  | Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age | 
| Periventricular Leukomalacia |  | Infant's entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age | 
| Mortality |  | Infant's entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age | 
| Intraventricular Hemorrhage |  | Infants entire inpatient record assessed at/after time of hospital discharge/transfer/death up until one year of age | 
| Daily weight gain in grams |  | Measured daily until time of hospital discharge/transfer/death up until one year of age | 
| Discharge weight measured and expressed by percentile of growth for age |  | Assessed at the time of discharge/transfer/death up until one year of age | 
| Length of Stay |  | Measured at time of discharge/transfer/death up until one year of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Feeding Tolerance, Extremely Low Birthweight Infants