Objective: Breast milk contains prebiotic oligosaccharides that promote enteral tolerance and intestinal colonisation with non-pathogenic bacteria. Many mothers delivering preterm are unable to provide sufficient milk. We conducted a UK multicentre randomised controlled trial of the effect of preterm formula containing 0.8% prebiotics (90% short chain galacto-oligosaccharides/10% long chain fructo-oligosaccharides, Immunofortis) on enteral tolerance. Primary outcomes were time to establish a total milk intake of 150 ml/kg per day and extent to which a total milk intake of ⩾150 ml/kg per day was tolerated between birth and term/discharge. Secondary outcomes included growth, fecal characteristics, gastrointestinal signs, necrotising enterocolitis and infection.
Methods: Infants were randomly assigned within 24 h of birth with stratification by gestational age and centre, to receive Nutriprem 1 (standard preterm formula) or Nutriprem 1 containing prebiotic oligosaccharides (trial formula), to augment insufficient maternal milk volume. Research ethics approval and written parent consent were obtained. The study was designed by the clinical investigators, sponsored and funded by Danone Research and overseen by independent data monitoring and steering committees. Randomisation and analyses were conducted at Imperial College London. Outcomes were adjusted for prespecified covariates.
Results: We recruited 160 appropriate for gestational age infants born <33 weeks gestation. There were no significant differences in baseline characteristics, time to tolerate 150 ml/kg per day or secondary outcomes. Significant benefit occurred in infants <29 weeks gestational age receiving trial formula with a 12.3% increase in the proportion of days between birth and term/discharge that a total daily milk intake of ⩾150 ml/kg was tolerated (p = 0.03).
Conclusion: Oligosaccharide (Immunofortis) supplementation improves enteral tolerance in extremely preterm infants.