Ng Derek Hang Cheong, Klassen Joel, Embleton Nicholas D, McGuire William
Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK.
Cochrane Database Syst Rev. 2017 Oct 2;10(10):CD012412. doi: 10.1002/14651858.CD012412.pub2.
When human milk is not available for feeding preterm infants, protein hydrolysate rather than standard cow's milk formulas (with intact proteins) are often used because they are perceived as being tolerated better and less likely to lead to complications. However, protein hydrolysate formulas are more expensive than standard formulas, and concern exists that their use in practice is not supported by high-quality evidence.
To assess the effect of feeding preterm infants with hydrolysed formula (versus standard cow's milk formulas) on the risk of feed intolerance, necrotising enterocolitis, and other morbidity and mortality in preterm infants.
We used the standard Cochrane Neonatal search strategy including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4), Ovid MEDLINE, Ovid Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to April 2017), as well as conference proceedings and previous reviews.
Randomised and quasi-randomised controlled trials that compared feeding preterm infants with protein hydrolysate versus standard (non-hydrolysed) cow's milk formula.
Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios and risk differences for dichotomous data, and mean differences for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in sensitivity analyses. We assessed quality of evidence at the outcome level using the GRADE approach.
We identified 11 trials for inclusion in the review. All trials were small (total participants 665) and had various methodological limitations including uncertainty about methods to ensure allocation concealment and blinding. Most participants were clinically stable preterm infants of gestational age less than about 34 weeks or birth weight less than about 1750 g. Fewer participants were extremely preterm, extremely low birth weight, or growth-restricted. Most trials found no effects on feed intolerance assessed variously as mean prefeed gastric residual volume, incidence of abdominal distention or other concerning gastrointestinal signs, or time taken to achieve full enteral feeds (meta-analysis was limited because studies used different measures). Meta-analysis found no effect on the risk of necrotising enterocolitis (typical risk ratio 1.10, 95% CI 0.36 to 3.34; risk difference 0.00, 95% CI -0.03 to 0.04; 5 trials, 385 infants) (low quality evidence; downgraded for imprecision and design weaknesses).
AUTHORS' CONCLUSIONS: The identified trials provide only low quality evidence about the effects of feeding preterm infants with protein hydrolysate versus standard formula. The existing data did not support conclusions that feeding with protein hydrolysate affects the risk of feed intolerance or necrotising enterocolitis. Further large, pragmatic trials are needed to provide more reliable and precise estimates of effectiveness and cost-effectiveness.
当无法用母乳喂养早产儿的时候，常使用蛋白质水解物而非标准牛奶配方奶粉（含完整蛋白质），因为人们认为前者耐受性更好，引发并发症的可能性更低。然而，蛋白质水解物配方奶粉比标准配方奶粉更昂贵，且有人担心在实际应用中缺乏高质量证据支持。
评估用水解配方奶粉（与标准牛奶配方奶粉相比）喂养早产儿对喂养不耐受、坏死性小肠结肠炎以及早产儿其他发病和死亡风险的影响。
我们采用了Cochrane新生儿标准检索策略，包括对Cochrane对照试验中央注册库（CENTRAL；2017年第4期）、Ovid MEDLINE、Ovid Embase以及护理和联合健康文献累积索引（CINAHL）（截至2017年4月）进行电子检索，以及检索会议论文集和以往的综述。
比较用蛋白质水解物与标准（非水解）牛奶配方奶粉喂养早产儿的随机和半随机对照试验。
两位综述作者独立评估试验的入选资格和偏倚风险，并提取数据。我们按照各个试验中的描述分析治疗效果，报告二分数据的风险比和风险差异，以及连续数据的均值差异，并分别给出95%置信区间（CI）。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究异质性的潜在原因。我们采用GRADE方法在结局层面评估证据质量。
我们确定了11项试验纳入本综述。所有试验规模都较小（总参与者共665名），且存在各种方法学上的局限性，包括确保分配隐藏和盲法的方法存在不确定性。大多数参与者是孕周小于约34周或出生体重小于约1750g的临床稳定早产儿。极早产儿、极低出生体重儿或生长受限儿的参与者较少。大多数试验发现，以不同方式评估的喂养不耐受没有受到影响，这些评估方式包括平均喂养前胃残余量、腹胀发生率或其他相关胃肠道体征，或实现完全肠内喂养所需的时间（由于研究使用不同的测量方法，荟萃分析受到限制）。荟萃分析发现对坏死性小肠结肠炎风险没有影响（典型风险比1.10，95%CI 0.36至3.34；风险差异0.00，95%CI -0.03至-0.04；5项试验，385名婴儿）（低质量证据；因不精确性和设计缺陷而降级）。
已识别的试验仅提供了低质量证据，证明用蛋白质水解物与标准配方奶粉喂养早产儿的效果。现有数据不支持以下结论：用蛋白质水解物喂养会影响喂养不耐受或坏死性小肠结肠炎的风险。需要进一步开展大规模、务实的试验，以更可靠、精确地评估有效性和成本效益。
