Westerbeek Elisabeth A M, van Elburg Ruurd M, van den Berg Anemone, van den Berg Jolice, Twisk Jos W R, Fetter Willem P F, Lafeber Harrie N
Department of Paediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, The Netherlands.
BMC Pediatr. 2008 Oct 23;8:46. doi: 10.1186/1471-2431-8-46.
Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.
METHODS/DESIGN: In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.
Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.
Current Controlled Trials ISRCTN16211826.
预防早产儿发生严重感染是一项挑战，因为早产和低出生体重常常需要进行多种干预措施且设备的使用频率很高。此外，由于胃肠道不成熟且免疫系统正在发育，进行肠内营养的可能性有限。与足月儿相比，肠道细菌定植延迟，这可能会增加发生严重感染的风险。酸性和中性低聚糖在免疫系统发育、肠道细菌定植以及肠道功能完整性方面发挥着重要作用。本试验旨在确定肠内补充酸性和中性低聚糖对早产儿感染性发病率（主要结局）、对免疫接种的免疫反应、喂养耐受性以及短期和长期结局的影响。此外，还试图阐明酸性和中性低聚糖在出生后免疫反应调节和肠道出生后适应中的作用。
方法/设计：在一项双盲安慰剂对照随机试验中，120名早产儿（胎龄<32周和/或出生体重<1500克）在出生后第3天至30天被随机分配接受肠内酸性和中性低聚糖补充剂（20%/80%）或安慰剂补充剂（麦芽糊精）。主要结局是感染性发病率（定义为严重感染的发生率）。通过测定对DTaP-IPV-Hib(-HBV)+PCV7免疫接种的免疫反应、血浆细胞因子浓度、粪便钙卫蛋白和白细胞介素-8来研究酸性和中性低聚糖在免疫反应调节中的作用。通过测量喂养耐受性、肠道通透性、肠道粘度以及确定肠道微生物群来研究肠内补充酸性和中性低聚糖对肠道出生后适应的影响。此外，还评估了短期和长期结局。
尤其是严重感染风险增加的早产儿，可能会从补充益生元中获益。大多数关于益生元的研究仅关注肠道微生物群的定植。然而，益生元影响免疫系统的途径尚未完全了解。由于早产儿感染存在多种危险因素，研究免疫调节作用很复杂。中性低聚糖与酸性低聚糖的组合可能对免疫系统具有更大的有益作用。深入了解益生元对发育中免疫系统的影响可能有助于降低早产儿的（感染性）发病率和死亡率。
当前受控试验ISRCTN16211826。
