Infloran® for Prevention of Necrotizing Enterocolitis

Oral Probiotics (Infloran®) for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Infants

Necrotizing enterocolitis (NEC) is one of the most devastating gastrointestinal emergencies in preterm neonates and a leading cause of death and morbidity.

The pathogenesis of NEC remains largely unclear, but it is widely considered as a multifactorial disease. Prematurity, enteral feeding, bacterial colonisation of the gut and intestinal ischemia have been proposed as major risk factors.

Probiotics may prevent NEC by improving the maturity and function of the gut mucosal barrier, modulating the immune system, promoting colonization of the gut with beneficial organisms and preventing colonization by pathogens.

A variety of clinical trials have evaluated the effect of different probiotic preparations on the occurrence of NEC in preterm infants. The results of recent metaanalyses suggest a benefit of probiotic bacteria in reducing the incidence of NEC and propose a change of practice.

The aim of the study is to evaluate the efficacy of the probiotic preparation Infloran® in reducing the incidence of NEC after implementation in clinical routine in preterm (< 34 weeks gestational age) very low birth weight infants compared to a historical cohort.

Study Overview

• Status: Completed
• Conditions: Necrotizing Enterocolitis

• Study Type: Observational
• Enrollment (Actual): 463

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University Vienna
  • Vienna, Austria, 1160
    • Wilheminenspital der Stadt Wien

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Very low birth weight Infants (<1500g birth weight)

Description

Inclusion Criteria:

• Neonates admitted to the neonatal intensive care unit on day 1 of life
• Very low birth weight (<1500 gram)
• Prematurity < 34/0 weeks gestational age
• For group receiving probiotics: 230 infants born after the 20/Sep/2010 (i.e. date of introduction of Infloran in clinical routine)
• For control group (historical): 230 infants born before 2010

Exclusion Criteria:

• Malformation of the gut (omphalocele, gastroschisis, intestinal atresia)
• Death before seven days of life, except due to NEC
• Transfer to another hospital before 37 weeks of corrected gestational age, except those who were transferred to a partner clinic using the same protocol for probiotic supplementation
• For group receiving probiotics: Infants who did not receive Infloran® starting in the first week of life or stopped before 34 weeks gestational age, except infants who developed NEC (reason for discontinuation of Infloran)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Probiotics (Infloran); Very low birth weight Infants receiving 2 capsules/d Infloran starting in the first week of life
Control; Very low birth weight Infants who did not receive Infloran (historical cohort)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of NEC	NEC stages 2 or 3 according to Bell´s modified staging of NEC	From birth to 37 weeks of gestational age (usually around 12 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Severity of NEC	From birth to 37 weeks of gestational age (usually around 12 weeks)
Influence of enteral feeding with human milk or formula on the incidence of NEC after the implementation of Infloran®	From birth to 37 weeks of gestational age (usually around 12 weeks)

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Wilheminenspital der Stadt Wien
• Investigators: Principal Investigator: Andreas Repa, MD, Medical University Vienna; Study Director: Nadja Haiden, MD, Medical University Vienna; Study Chair: Margarita Thanhäuser, MD, Medical University Vienna

Publications and helpful links

General Publications

• Repa A, Thanhaeuser M, Endress D, Weber M, Kreissl A, Binder C, Berger A, Haiden N. Probiotics (Lactobacillus acidophilus and Bifidobacterium infantis) prevent NEC in VLBW infants fed breast milk but not formula [corrected]. Pediatr Res. 2015 Feb;77(2):381-8. doi: 10.1038/pr.2014.192. Epub 2014 Nov 25. Erratum In: Pediatr Res. 2016 Jan;79(1-1):124.

Helpful Links

• Homepage Medical University Vienna

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): October 1, 2012

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (ESTIMATE): December 18, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Probiotics; Necrotizing Enterocolitis; Very Low Birth Weight Infants
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: MUV-Neo3