Morgan Jessie, Young Lauren, McGuire William
Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK.
Cochrane Database Syst Rev. 2014(12):CD001241. doi: 10.1002/14651858.CD001241.pub5. Epub 2014 Dec 2.
Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis 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 necrotising enterocolitis. However, slow feed advancement may delay establishment of full enteral feeding and be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition.
To determine the effect of slow rates of enteral feed advancement on the incidence of necrotising enterocolitis, mortality, and other morbidities in very preterm or VLBW infants.
We used the standard search strategy of the Cochrane Neonatal Review Group Specialised Register. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 8), MEDLINE, EMBASE, and CINAHL (to September 2014), conference proceedings, and previous reviews.
Randomised or quasi-randomised controlled trials that assessed the effect of slow (up to 24 ml/kg per day) versus faster rates of advancement of enteral feed volumes upon the incidence of necrotising enterocolitis in very preterm or VLBW infants.
Two review authors independently assessed trial eligibility and risk of bias and undertook data extraction. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals. We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses.
We identified six randomised controlled trials in which a total of 618 infants participated. Most participants were stable preterm infants of birth weight between 1000 g and 1500 g. Few participants were extremely preterm, extremely low birth weight, or growth-restricted. The trials typically defined slow advancement as daily increments of 15 ml/kg to 20 ml/kg and faster advancement as 30 ml/kg to 35 ml/kg. Meta-analyses did not detect statistically significant effects on the risk of necrotising enterocolitis (typical risk ratio (RR) 0.96, 95% confidence interval (CI) 0.55 to 1.70) or all-cause mortality (typical RR 1.57, 95% CI 0.92 to 2.70). Infants who had slow advancement took significantly longer to regain birth weight (reported median differences 2 to 6 days) and to establish full enteral feeding (1 to 5 days).
AUTHORS' CONCLUSIONS: The available trial data suggest that advancing enteral feed volumes at daily increments of 30 ml/kg to 35 ml/kg does not increase the risk of necrotising enterocolitis in very preterm or VLBW infants. Advancing the volume of enteral feeds at slow rates resulted in several days delay in regaining birth weight and establishing full enteral feeds. The applicability of these findings to extremely preterm, extremely low birth weight, or growth-restricted infants is limited. Further randomised controlled trials in these populations may be warranted to resolve this uncertainty.
早期肠内喂养方式可能是极早产儿或极低出生体重(VLBW)儿坏死性小肠结肠炎的潜在可改变风险因素。观察性研究表明,保守的喂养方案,包括缓慢增加肠内喂养量,可降低坏死性小肠结肠炎的风险。然而,缓慢增加喂养量可能会延迟完全肠内喂养的建立,并与长期接受肠外营养继发的代谢和感染性疾病相关。
确定缓慢增加肠内喂养量对极早产儿或VLBW儿坏死性小肠结肠炎发病率、死亡率及其他疾病的影响。
我们采用了Cochrane新生儿综述组专业注册库的标准检索策略。检索了Cochrane对照试验中心注册库(CENTRAL 2014年第8期)、MEDLINE、EMBASE和CINAHL(截至2014年9月)、会议论文集及以往的综述。
随机或半随机对照试验,评估缓慢(每天最多24 ml/kg)与较快增加肠内喂养量对极早产儿或VLBW儿坏死性小肠结肠炎发病率的影响。
两位综述作者独立评估试验的合格性和偏倚风险,并进行数据提取。我们分析了各个试验的治疗效果,报告了二分数据的风险比和风险差以及连续数据的均值差,并给出各自的95%置信区间。我们在荟萃分析中使用固定效应模型,并在敏感性分析中探讨异质性的潜在原因。
我们确定了6项随机对照试验,共有618名婴儿参与。大多数参与者是出生体重在1000 g至1500 g之间的稳定早产儿。极少有参与者是极早产儿、极低出生体重儿或生长受限儿。试验通常将缓慢增加定义为每天增加15 ml/kg至20 ml/kg,较快增加定义为30 ml/kg至35 ml/kg。荟萃分析未发现对坏死性小肠结肠炎风险(典型风险比(RR)0.96,95%置信区间(CI)0.55至1.70)或全因死亡率(典型RR 1.57,95% CI 0.92至2.70)有统计学显著影响。缓慢增加喂养量的婴儿恢复出生体重(报告的中位数差异为2至6天)和建立完全肠内喂养(1至5天)所需的时间明显更长。
现有试验数据表明,以每天30 ml/kg至35 ml/kg的增量增加肠内喂养量不会增加极早产儿或VLBW儿坏死性小肠结肠炎的风险。缓慢增加肠内喂养量会导致恢复出生体重和建立完全肠内喂养延迟数天。这些发现对极早产儿、极低出生体重儿或生长受限儿的适用性有限。可能需要在这些人群中进一步开展随机对照试验以解决这一不确定性。