Neurodevelopment of preterm infants at 24 months after neonatal supplementation of a prebiotic mix: A randomized trial

Objectives: Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period may further harm neurodevelopmental outcomes. The present study aimed to determine the effect of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) on neurodevelopmental outcomes measured by Bayley Scales of Infant and Toddler Development in preterm infants at 24 months. Methods: In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3 and 30 of life. Serum samples at day 1, 7, and 14 were analyzed for cytokine levels. Stool samples at day 1, 7, 14, and 30 were measured for bacterial count and bifidobacteria percentage. At 24 months corrected age infants were followed up by a blinded pediatric psychologist for the Bayley Scales of Infant and Toddler Development II or III. Results: Seventy-seven of one hundred one (76%) eligible infants participated in the follow-up study. Neurodevelopmental outcomes were not different in the scGOS/lcFOS/pAOS and placebo group. Infections during the neonatal period, lower percentages of bifidobacteria at day 7 (F=3.8, P=0.05) and day 14 (F=5.0, P=0.02) and higher levels of Interleukine (IL)-1β (F=4.0, P=0.04) and IL-8 (F=8.0, P=0.01) at day 7 are associated with lower mental developmental index. Lower psychomotor outcomes are associated with IL-2 (F=4.0, P=0.05), IL-4 (F=6.0, P=0.02) at birth, and interferon gamma at day 7 (F=4.4, P=0.04). Conclusions: scGOS/lcFOS/pAOS showed no significant improvement of neurodevelopmental outcomes at 24 months in preterm infants. Infections, lower bifidobacteria counts, and higher serum cytokine levels during the neonatal period were associated with lower neurodevelopmental outcomes at 24 months of age indicating the relevance of microbiome and immune responses in neurodevelopmental processes.