Neurodevelopment of Preterm infants at 24 Month After Neonatal Supplementation of a Prebiotic Mix: A Randomized Trial

Abstract

OBJECTIVES: Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period might further harm neurodevelopmental outcomes. This 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 (BSID) in preterm infants at 24 months. METHODS: In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3-30 of life. Serum samples at day 1, 7, 14 were analysed 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 BSID II or III. RESULTS: 77/101 (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.