Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Department of Neonatal Medicine, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Cochrane Database Syst Rev. 2021 Aug 24;8(8):CD001241. doi: 10.1002/14651858.CD001241.pub8.
BACKGROUND: Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. However, it is unclear whether slow feed advancement may delay establishment of full enteral feeding, and if it could be associated with infectious morbidities secondary to prolonged exposure to parenteral nutrition. OBJECTIVES: To determine the effects of slow rates of enteral feed advancement on the risk of NEC, mortality, and other morbidities in very preterm or VLBW infants. SEARCH METHODS: We searched CENTRAL (2020, Issue 10), Ovid MEDLINE (1946 to October 2020), Embase via Ovid (1974 to October 2020), Maternity and Infant Care database (MIDIRS) (1971 to October 2020), CINAHL (1982 to October 2020), and clinical trials databases and reference lists of retrieved articles for eligible trials. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes on the risk of NEC in very preterm or VLBW infants. DATA COLLECTION AND ANALYSIS: Two review authors separately evaluated trial risk of bias, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence. Outcomes of interest were NEC, all-cause mortality, feed intolerance, and invasive infection. MAIN RESULTS: We included 14 trials involving a total of 4033 infants (2804 infants participated in one large trial). None of the trials masked parents, caregivers, or investigators. Risk of bias was otherwise low. Most infants were stable very preterm or VLBW infants of birth weight appropriate for gestation. About one-third of all infants were extremely preterm or extremely low birth weight (ELBW), and about one-fifth were small for gestational age, growth-restricted, or compromised as indicated by absent or reversed end-diastolic flow velocity in the foetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 24 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Meta-analyses showed that slow advancement of enteral feed volumes probably has little or no effect on the risk of NEC (RR 1.06, 95% confidence interval (CI) 0.83 to 1.37; RD 0.00, 95% CI -0.01 to 0.02; 14 trials, 4026 infants; moderate-certainty evidence) or all-cause mortality prior to hospital discharge (RR 1.13, 95% CI 0.91 to 1.39; RD 0.01, 95% CI -0.01 to 0.02; 13 trials, 3860 infants; moderate-certainty evidence). Meta-analyses suggested that slow advancement may slightly increase feed intolerance (RR 1.18, 95% CI 0.95 to 1.46; RD 0.05, 95% CI -0.02 to 0.12; 9 trials, 719 infants; low-certainty evidence) and may slightly increase the risk of invasive infection (RR 1.14, 95% CI 0.99 to 1.31; RD 0.02, 95% CI -0.00 to 0.05; 11 trials, 3583 infants; low-certainty evidence). AUTHORS' CONCLUSIONS: The available trial data indicate that advancing enteral feed volumes slowly (daily increments up to 24 mL/kg) compared with faster rates probably does not reduce the risk of NEC, death, or feed intolerance in very preterm or VLBW infants. Advancing the volume of enteral feeds at a slow rate may slightly increase the risk of invasive infection.
背景:早期肠内喂养方案可能是极低出生体重儿(VLBW)或极早产儿发生坏死性小肠结肠炎(NEC)的可改变的危险因素。观察性研究表明,包括缓慢增加肠内喂养量在内的保守喂养方案可降低 NEC 的风险。但是,目前尚不清楚缓慢的喂养进度是否会延迟完全肠内喂养的建立,以及它是否可能与由于长期接受肠外营养而导致的感染性发病率增加有关。
目的:确定以较慢速度增加肠内喂养量对极低出生体重儿或极早产儿 NEC、死亡率和其他并发症的影响。
检索方法:我们检索了 Cochrane 中心对照试验数据库(2020 年第 10 期)、Ovid MEDLINE(1946 年至 2020 年 10 月)、ovid Embase(1974 年至 2020 年 10 月)、Maternity and Infant Care 数据库(1971 年至 2020 年 10 月)、CINAHL(1982 年至 2020 年 10 月)和临床试验数据库,并查阅了检索到的文章的参考文献列表,以获取合格试验的信息。
入选标准:我们纳入了评估较慢(高达 24 mL/kg/d)与较快(每天增加 30-40 mL/kg)肠内喂养量速度增加对极低出生体重儿或极早产儿发生 NEC 风险影响的随机或半随机对照试验。
数据收集与分析:两位综述作者分别评估了试验的偏倚风险、提取数据,并使用风险比(RR)、风险差(RD)和均数差(MD)来综合效应估计值。我们使用 GRADE 方法评估证据的确定性。感兴趣的结局包括 NEC、全因死亡率、喂养不耐受和侵袭性感染。
主要结果:我们纳入了 14 项试验,共涉及 4033 名婴儿(2804 名婴儿参加了一项大型试验)。这些试验均未对父母、照顾者或研究者进行盲法处理。其他偏倚风险较低。大多数婴儿是稳定的极早产儿或 VLBW 婴儿,胎龄适宜出生体重。大约三分之一的婴儿是极早产儿或极低出生体重儿(ELBW),大约五分之一的婴儿是小于胎龄儿、生长受限儿或因胎儿脐动脉舒张末期血流速度缺失或反转而存在潜在的或已经发生的血流受限。试验通常将缓慢的肠内喂养量增加定义为每天增加 15-24 mL/kg,而较快的增加则定义为每天增加 30-40 mL/kg。荟萃分析显示,缓慢增加肠内喂养量可能对 NEC 的风险(RR 1.06,95%置信区间(CI)0.83 至 1.37;RD 0.00,95%CI -0.01 至 0.02;14 项试验,4026 名婴儿;中等确定性证据)或全因死亡率(RR 1.13,95%CI 0.91 至 1.39;RD 0.01,95%CI -0.01 至 0.02;13 项试验,3860 名婴儿;中等确定性证据)影响很小或没有。荟萃分析提示,缓慢增加喂养量可能略微增加喂养不耐受(RR 1.18,95%CI 0.95 至 1.46;RD 0.05,95%CI -0.02 至 0.12;9 项试验,719 名婴儿;低确定性证据)和侵袭性感染的风险(RR 1.14,95%CI 0.99 至 1.31;RD 0.02,95%CI -0.00 至 0.05;11 项试验,3583 名婴儿;低确定性证据)。
作者结论:现有试验数据表明,与较快的速度相比,以较慢的速度(每天增加量高达 24 mL/kg)增加肠内喂养量可能不会降低极低出生体重儿或极早产儿的 NEC、死亡或喂养不耐受的风险。以较慢的速度增加肠内喂养量可能会略微增加侵袭性感染的风险。
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