Prebiotic supplementation in preterm neonates: updated systematic review and meta-analysis of randomised controlled trials.

BACKGROUND & AIMS Regular administration of prebiotic oligosaccharides promote beneficial gut flora in infants. We aimed to systematically review randomized controlled trials evaluating the safety and efficacy of prebiotic oligosaccharide supplementation in preterm infants ≤ 37 weeks of gestation. METHODS Available studies from Medline, Embase, comparing formula milk supplemented with or without prebiotics, reporting on safety and the incidence of necrotising enterocolitis (NEC), late onset sepsis, feed tolerance, physical growth and various stool characteristics were eligible. RESULTS 7 trials (n = 417) were included. Five trials (n = 345) reported on the incidence of NEC, 3 trials (n = 295) reported on the incidence of late onset sepsis. Meta-analysis revealed a pooled RR (95% CI) of 1.24 (0.56-2.72) for NEC, 0.81 (0.57-1.15), p 0.23 for the risk of late onset sepsis. 3 individual trials (n = 295) did not observe any improvement in time to enteral feeds post intervention. Meta-analysis indicated a statistically significant difference in the growth of bifidobacteria in the oligosaccharide group with a weighted mean difference of 0.53 (95% CI: 0.33, 0.73) *10(6) colonies/g, p < 0.00001. A reduction in stool viscosity and pH was also observed. None of the trials reported life threatening adverse effects. CONCLUSIONS Supplementation with prebiotic oligosaccharides was safe and did not result in decreased incidence of NEC, late onset sepsis and time to full enteral feeds but resulted in a significantly higher growth of beneficial microbes.