Prophylactic Probiotics to Extremely Low Birth Weight Prematures
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Feeding; Difficult, Newborn
- Sponsor
- Ostergotland County Council, Sweden
- Enrollment
- 134
- Locations
- 2
- Primary Endpoint
- Time to Establish Full Enteral Feeds
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis, and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition.
The aim of the study is to evaluate whether supplementation with the probiotic bacterium Lactobacillus reuteri DSM 17938 daily to premature infants with extremely low birth weight increases feeding tolerance to breast milk and thereby improves nutrition, increases growth and reduces serious complications and mortality in this population. Beyond this, possible mechanisms underlying these effects will be analyzed in stool, breast milk and blood samples.
Detailed Description
RATIONALE Mortality and incidence of severe complications is still high among extremely premature infants. Common causes of severe complications in this population are poor nutrition, necrotizing enterocolitis (NEC), and severe infections. Feeding intolerance is also a common problem resulting in prolonged need for intravenous lines and poor nutrition. There is scientific evidence that dietary supplements with probiotics may have an effect on these manifestations. Lactobacillus reuteri is a well studied probiotic bacterium that has been tested in several clinical studies in premature infants and older children, and the results of these studies and animal studies suggest that this bacterium may also have an effect on growth and mortality in extremely premature infants. Lactobacillus reuteri reduces colonization with pathogenic microbes, stimulates gastric and intestinal motility and shortens hospital stay in moderately premature infants. In animal models, L. reuteri also induces anti-inflammatory immune responses, reduces the symptoms of inflammatory bowel disease and the incidence of NEC. Administration of L. reuteri also improves the intestinal barrier both in human studies in children and in animal studies. Dietary supplements of L. reuteri to extremely premature infants may therefore improve feeding tolerance and nutrition and reduce the incidence of severe complications in this population. HYPOTHESIS Premature infants with extremely low birth weight receiving daily supplements of Lactobacillus reuteri DSM 17938 will reach full enteral feeding faster compared with children receiving placebo. STUDY DESIGN This study will be conducted as a prospective multi-center double blind placebo-controlled study in neonatal intensive care units in Sweden. In total 134 neonates with extremely low birth weight (\<1000g) and gestational age \<28+0 weeks will be randomized to receive either dietary supplements of Lactobacillus reuteri or placebo. Study product will be identical to the active and placebo group besides the addition of Lactobacillus reuteri (1.25 x 100 million bacteria=0.2 ml oil drops per day) in the active group. The supplementation will commence within 1-3 days after birth and will be given daily until gestational week 36+0. The infants will be followed until gestational week 36+0 and data on feeding tolerance, nutrition, growth, infections, NEC, bronchopulmonary dysplasia, death, and potential confounders will be entered in an individual study protocol. Stool, breast milk, and blood samples will be collected for analyses of possible underlying mechanisms. A 2-year follow up including examination by pediatrician, growth parameters, questionnaire and psychology testing (Bayley´s test) will be performed.
Investigators
Thomas Abrahamsson, MD, PhD
MD, PhD, Neonatologist
Ostergotland County Council, Sweden
Eligibility Criteria
Inclusion Criteria
- •Birth weight \< 1000 g
- •Gestational age: v23+0-V27 +
- •Age \< 72 hours at inclusion.
- •Signed informed consent by parents.
Exclusion Criteria
- •Fatal or complex congenital malformation at inclusion time.
- •Chromosomal defect at inclusion time.
- •No realistic hope of survival at inclusion time.
- •Gastrointestinal malformation at inclusion time.
- •Participation in another study which aims to influence nutrition, growth, feeding tolerance or necrotizing enterocolitis.
Outcomes
Primary Outcomes
Time to Establish Full Enteral Feeds
Time Frame: Birth to gestational week 36+0
The age of the infants in days when the infant receive 150 ml/kg/day via enteral feeding for the first time.
Secondary Outcomes
- Time Until Birth Weight is Regained. Specifies the Number of Full Days the Child Has Lived.(Birth to gw 36+0)
- Sepsis(Birth to gw 36+0)
- Days With Halted Feeding Due to Food Intolerance(Birth to gestational week 36)
- Weight Gain (SD)(At gestational week 36+0)
- Mortality(Birth to gw 36+0)
- Necrotizing Enterocolitis(Birth to gw 36+0)
- Bronchopulmonary Dysplasia(Gw 36+0)
- Neurological Development Impairment(At 2 years corrected age)
- Number of Stools(Recorded over the first four weeks)
- Head Circumference Growth (SD)(At gestational week 36+0)
- Length Gain (SD)(At gestational week 36+0)
- Neurological Development(At 2 years corrected age)