Prophylactic Probiotics to Extremely Low Birth Weight Prematures
Condition: Feeding; Difficult, Newborn; Growth Failure; Necrotizing Enterocolitis; Sepsis
MeSH terms: Enterocolitis; Enterocolitis, Necrotizing; Premature Birth; Birth Weight; Failure to Thrive
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Lactobacillus reuteri; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Oil drops with Lactobacillus reuteri DSM 17938, 125 million bacteria=0.2 ml per day; Oil drops without Lactobacillus reuteri
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Probiotics; Lactobacillus reuteri; Prematures; Enteral feeding; Motility; Necrotizing enterocolitis; Sepsis; Weight