Medically-Graded Honey Supplementation Formula To Preterm Infants (Honey)

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

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.

Study Overview

• Status: Completed
• Conditions: Premature Infants; Intestinal Microbiota; Prebiotics; Honey
• Intervention / Treatment: Other: Premature Milk Formula; Dietary supplement: Medically-Graded Honey

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 3 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• Boyar V, Handa D, Clemens K, Shimborske D. Clinical experience with Leptospermum honey use for treatment of hard to heal neonatal wounds: case series. J Perinatol. 2014 Feb;34(2):161-3. doi: 10.1038/jp.2013.158.
• Eteraf-Oskouei T, Najafi M. Traditional and modern uses of natural honey in human diseases: a review. Iran J Basic Med Sci. 2013 Jun;16(6):731-42.
• Ezz El-Arab AM, Girgis SM, Hegazy EM, Abd El-Khalek AB. Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice. BMC Complement Altern Med. 2006 Mar 14;6:6. doi: 10.1186/1472-6882-6-6.
• Kapiki A, Costalos C, Oikonomidou C, Triantafyllidou A, Loukatou E, Pertrohilou V. The effect of a fructo-oligosaccharide supplemented formula on gut flora of preterm infants. Early Hum Dev. 2007 May;83(5):335-9. doi: 10.1016/j.earlhumdev.2006.07.003. Epub 2006 Sep 14.
• Aly H, Said RN, Wali IE, Elwakkad A, Soliman Y, Awad AR, Shawky MA, Alam MSA, Mohamed MA. Medically Graded Honey Supplementation Formula to Preterm Infants as a Prebiotic: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2017 Jun;64(6):966-970. doi: 10.1097/MPG.0000000000001597.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: February 9, 2016
• First Posted (Estimate): February 10, 2016

Study Record Updates

• Last Update Posted (Estimate): February 10, 2016
• Last Update Submitted That Met QC Criteria: February 9, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 100904