Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis

Study Overview
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Brief Summary
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Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC.

Detailed Description
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Preterm neonates, <1500 gm birth weight will potentially be candidates for study and will be recruited when they begin enteral feeding. The infants will be prospectively and randomly assigned to one of two groups: Treatment group - to receive daily inactivated probiotic prophylaxis starting with the initiation of feeds. 1 tsp powder will be diluted in 2 cc of mother's milk when possible or in Similac Special Care formula 24 cal when mother's milk is not available; and Control group - to receive 2 cc/day of placebo similarly diluted. Supplements will be continued until the infant tolerates enteral feeds of 100 cc/kg/day or reaches 35 weeks post conceptual age (whichever comes LAST). Biotikid, a probiotic mixture, will be heated to 100 degrees C for 10 minutes. Babies will be followed clinically for signs of NEC, and with urine intestinal fatty acid binding protein (IFABP) and fecal calprotectin levels. The investigators primary aim is to demonstrate that premature neonates who are treated prophylactically with heat inactivated probiotics will have less necrotizing enterocolitis when compared to age matched infants given placebo. The investigators secondary objectives are to demonstrate the following: That the decrease in NEC will coincide with improved intestinal barrier integrity, as reflected by levels of: I-FABP in urine Fecal Calprotectin

Official Title
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Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates

Conditions
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Necrotizing Enterocolitis, Enterocolitis, Necrotizing

Intervention / Treatment
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* Dietary Supplement: Heat Inactivated probiotics
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm neonates ≤1500 gm birth weight Exclusion Criteria: Infants who are not deemed likely to survive more than one week; Infants who are not started on enteral feeds by one week of age; Infants who have significant congenital malformations or other gastrointestinal problem

Ages Eligible for Study
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Minimum Age: 6 Hours
Maximum Age: 7 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Dietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula. | Dietary Supplement: Placebo<br>* 2 cc of milk will be given to control group<br>|
| Active Comparator: Treatment Group<br>Dietary Supplement: Heat Inactivated Probiotics 1 tsp heat inactivated Biotikid powder will be diluted in 2 cc of mother's milk (when available) or premature formula. | Dietary Supplement: Heat Inactivated probiotics<br>* Biotikid, a probiotic mixture, will be heated to 100 degrees Centigrade for 10 minutes to inactivate and then 1 tsp will be diluted in milk and give with feeds to treatment group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Necrotizing Enterocolitis, Bell Stage 2 or above, or Death | Necrotizing Enterocolitis diagnosis will be based on clinical and radiographic criteria | Birth until 40 weeks post-conceptional age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased Urine IFABP Levels |  | Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age | 
| Increased Fecal Calprotectin Levels |  | Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age |