Evaluation of Safety, Tolerance and Effects on the Intestinal Flora of a New Fermented Milk for Preterm Infants

Evaluation of a Fermented Formula Without Live Bacteria for Preterm Infants: Effects on Microbiota Species and Intestinal Inflammatory Markers

The intestinal flora is a complex ecosystem which is known to play various important functions in the gut. Recent data have reported a delay in intestinal colonization in preterm. Modulating the intestinal flora through dietary supplementation with probiotics or prebiotics has been shown to improve digestive and general outcomes in full-term infants.The aim of this study was to evaluate the clinical tolerance, the effect on gut microbiota, and the mucosal inflammatory responses to a fermented milk in preterm infants.

Study Overview

• Status: Completed
• Conditions: Preterms With Gestational Age Ranging From 30 to 35 Weeks
• Intervention / Treatment: Dietary supplement: Milk with probiotic and prebiotic activities; Dietary supplement: Milk without probiotic and prebiotic activities

Detailed Description

This prospective, randomized, double-blind, controlled study evaluated the safety and effect on gut microbiota, and the mucosal inflammatory responses to a fermented milk in preterm infants. Preterm infants with a gestational age (GA) ranging from 30 to 35 weeks and whose mother chose formula feeding were enrolled during their first three days of life. Both parents provided informed written consent. Infants were randomly assigned to receive either the fermented preterm formula (FPF) or, as a control, a formula adapted for preterm infants (PF). The PF was formulated to meet the nutritional needs of preterm infants. The FPF was identical, except for a manufacturing process including a fermentation step with two probiotic strains, Bifidobacterium breve C50 and Streptococcus thermophilus 065, inactivated by heat at the end of the manufacturing process. This process conferred a probiotic/prebiotic activity.For each neonate, background information about the pregnancy and neonatal parameters were collected. Anthropometric parameters (weight, height, head circumference); gastrointestinal tolerance parameters (abdominal distension, gastric residuals, rectal bleeding, NEC); drug administration; and intake of formula and mother's milk were recorded twice a week until discharge. Stools were collected twice a week from diapers for microbiological analysis and measurement of fecal inflammatory markers. All samples were immediately stored at -80°C.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Neonatat unit, Saint Vincent de Paul Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Preterms with gestational age ranging from 30 to 35 weeks
• Eutrophic
• Formula feeding

Exclusion Criteria:

• Malformation or metabolic disease
• Newborns whose parents did not provide informed consent
• Contraindication to enteral feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; the fermented preterm formula (FPF)	Dietary supplement: Milk with probiotic and prebiotic activities; Comparison of two different formula for preterm infants
Placebo Comparator: 2; formula adapted for preterm infants (PF)	Dietary supplement: Milk without probiotic and prebiotic activities; Comparison of formula for preterm infants; Other Names: Comparison of formula for preterm infants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Follow-up of the number of colonized infants and the bacterial colonization levels	weekly until hospital discharge

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical tolerance	weekly until hospital discharge
Levels of intestinal immune and inflammatory markers	weekly until hospital discharge

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Blédina SA, Villefranche sur Saône, France
• Investigators: Principal Investigator: Florence Campeotto, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Campeotto F, Waligora-Dupriet AJ, Doucet-Populaire F, Kalach N, Dupont C, Butel MJ. [Establishment of the intestinal microflora in neonates]. Gastroenterol Clin Biol. 2007 May;31(5):533-42. doi: 10.1016/s0399-8320(07)89424-3. French.

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): June 1, 2007

Study Registration Dates

• First Submitted: July 4, 2008
• First Submitted That Met QC Criteria: July 4, 2008
• First Posted (Estimate): July 9, 2008

Study Record Updates

• Last Update Posted (Estimate): July 9, 2008
• Last Update Submitted That Met QC Criteria: July 4, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: infant,; calprotectin; Premature birth,; infant formula,; bacterial colonization,; Bifidobacterium,
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 1977/06-05-02