van den Berg Jolice P, Westerbeek Elisabeth A M, Bröring-Starre Tinka, Garssen Johan, van Elburg Ruurd M
*Department of Paediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, The Netherlands †Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago ‡Department of Medical Psychology, VU University Medical Center, Amsterdam §Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences ||Nutricia Research, Utrecht ¶Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):270-6. doi: 10.1097/MPG.0000000000001148.
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.
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.
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).
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.
早产会破坏胎儿大脑成熟。新生儿期的炎症可能会进一步损害神经发育结局。本研究旨在确定短链低聚半乳糖/长链低聚果糖/果胶衍生酸性寡糖（scGOS/lcFOS/pAOS）对24个月大的早产儿通过贝利婴幼儿发育量表测量的神经发育结局的影响。
在这项随机对照试验中，在出生后第3天至第30天补充scGOS/lcFOS/pAOS或安慰剂。分析第1、7和14天的血清样本中的细胞因子水平。测量第1、7、14和30天的粪便样本中的细菌计数和双歧杆菌百分比。在24个月校正年龄时，由一位盲法儿科心理学家对婴儿进行贝利婴幼儿发育量表第二版或第三版的随访。
101名符合条件的婴儿中有77名（76%）参与了随访研究。scGOS/lcFOS/pAOS组和安慰剂组的神经发育结局没有差异。新生儿期感染、第7天（F = 3.8，P = 0.05）和第14天（F = 5.0，P = 0.02）双歧杆菌百分比降低以及第7天白细胞介素（IL）-1β水平升高（F = 4.0，P = 0.04）和IL-8水平升高（F = 8.0，P = 0.01）与较低的智力发育指数相关。较低的心理运动结局与出生时的IL-2（F = 4.0，P = 0.05）、IL-4（F = 6.0，P = 0.02）以及第7天的干扰素γ（F = 4.4，P = 0.04）相关。
scGOS/lcFOS/pAOS在24个月时对早产儿的神经发育结局没有显著改善。新生儿期感染、双歧杆菌计数降低和血清细胞因子水平升高与24个月时较低的神经发育结局相关，表明微生物群和免疫反应在神经发育过程中的相关性。
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