Medically-Graded Honey Supplementation Formula To Preterm Infants

Study Overview
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Brief Summary
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Honey is a natural product that contains multiple nutrients; it is composed of fructose, glucose and fructooligosaccharides that can potentially serve prebiotic functions. It also contains more than 180 substances including amino acids, vitamins, minerals and enzymes. Investigators hypothesized that supplementation of enteral feeds with honey would produce a bifidogenic effect and stimulate the immune response in preterm infants. Investigators randomly assigned subjects to 4 groups receiving 0, 5, 10 and 15 grams of honey daily for 2 weeks and measured their effect on stool colonization, systemic immune parameters and anthropometric measurements.

Official Title
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Randomized Controlled Trial on Medically-Graded Honey Supplementation Formula (As a Prebiotic) To Preterm Infants

Conditions
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Prebiotics, Honey, Premature Infants, Intestinal Microbiota

Intervention / Treatment
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* Dietary Supplement: Medically-Graded Honey
* Other: Premature Milk Formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preterm infants with gestational age ≤ 34 weeks postnatal age > 3 days no previous enteral feeding, and parental wish to use milk formula with no intention to use breast milk or breastfeed. Exclusion Criteria: infants with major chromosomal abnormalities Infant with major congenital anomalies of the cardiovascular, pulmonary or central nervous system; including neuromuscular disorders and neural tube defects infants with intestinal atresia, tracheoesophageal fistulas, omphalocele, gastroschisis, and other major congenital GI anomalies, and infants with sepsis, either before or during enrollment

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 3 Weeks

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control 0<br>No Intervention. This group received Premature Milk Formula. This group did not receive any Medically-Graded Honey. | Other: Premature Milk Formula<br>* Enteral feeds were provided to subjects of all groups using premature milk formula as per routine nutritional management in the neonatal intensive care unit.<br>|
| Experimental: Group 1<br>This group received Premature Milk Formula. This group received Medically-Graded Honey (dose = 5 gram/day) for 2 weeks | Dietary Supplement: Medically-Graded Honey<br>* Honey added to the baby formula once a day for 2 weeks.<br>Other: Premature Milk Formula<br>* Enteral feeds were provided to subjects of all groups using premature milk formula as per routine nutritional management in the neonatal intensive care unit.<br>|
| Experimental: Group 2<br>This group received Premature Milk Formula. This group received Medically-Graded Honey (dose = 10 gram/day) for 2 weeks | Dietary Supplement: Medically-Graded Honey<br>* Honey added to the baby formula once a day for 2 weeks.<br>Other: Premature Milk Formula<br>* Enteral feeds were provided to subjects of all groups using premature milk formula as per routine nutritional management in the neonatal intensive care unit.<br>|
| Experimental: Group 3<br>This group received Premature Milk Formula. This group received Medically-Graded Honey (dose = 15 gram/day) for 2 weeks | Dietary Supplement: Medically-Graded Honey<br>* Honey added to the baby formula once a day for 2 weeks.<br>Other: Premature Milk Formula<br>* Enteral feeds were provided to subjects of all groups using premature milk formula as per routine nutritional management in the neonatal intensive care unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The presence of Bifidobacterium bifidum and Lactobacillus spp in Stool | Stool culture/ Gram Stain and quantitative real time PCR were used to for this outcome. | Two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 and CD8 concentration in the serum | Serum concentrations of CD4 and CD8 cytokines were measured by by ELISA | 2 weeks | 
| Change in Weight (gram) | The difference between weight at enrollment and at 2 weeks was measured for all subjects | Baseline and 2 weeks | 
| Change in crown-heel length (cm) | The difference between the length at enrollment and at 2 weeks was measured for all subjects | Baseline and 2 weeks | 
| Change in head circumference (cm) | The difference between head circumference at enrollment and at 2 weeks was measured for all subjects | Baseline and 2 weeks |