Amissah Emma A, Brown Julie, Harding Jane E
Liggins Institute, University of Auckland, Auckland, New Zealand.
Cochrane Database Syst Rev. 2018 Aug 23;8(8):CD000280. doi: 10.1002/14651858.CD000280.pub2.
Preterm infants are born with low glycogen stores and require higher glucose intake to match fetal accretion rates. In spite of the myriad benefits of breast milk for preterm infants, it may not adequately meet the needs of these rapidly growing infants. Supplementing human milk with carbohydrates may help. However, there is a paucity of data on assessment of benefits or harms of carbohydrate supplementation of human milk to promote growth in preterm infants. This is a 2018 update of a Cochrane Review first published in 1999.
To determine whether human milk supplemented with carbohydrate compared with unsupplemented human milk fed to preterm infants improves growth, body composition, and cardio-metabolic and neurodevelopmental outcomes without significant adverse effects.
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to 21 February 2018), Embase (1980 to 21 February 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 21 February 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials.
Published and unpublished controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants in hospital fed human milk to supplementation or no supplementation with additional carbohydrate.
Two review authors independently abstracted data and assessed trial quality and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We planned to perform meta-analyses using risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. We contacted study authors for additional information.
One unblinded, quasi-randomised controlled trial (RCT) assessing effects of carbohydrate supplementation of human milk in the form of a prebiotic in 75 preterm infants was eligible for inclusion in this review. We identified two publications of the same trial, which reported different methods regarding blinding and randomisation. Study authors confirmed that these publications pertain to the same trial, but they have not yet clarified which method is correct. We were unable to reproduce analyses from the data presented. At 30 days of age, the mean weight of preterm infants in the trial was greater in the prebiotic carbohydrate-supplemented group than in the unsupplemented group (MD 160.4 grams, 95% CI 12.4 to 308.4 grams; one RCT, N = 75; very low-quality evidence). We found no evidence of a clear difference in risk of feeding intolerance (RR 0.64, 95% CI 0.36 to 1.15; one RCT, N = 75 infants; very low-quality evidence) or necrotising enterocolitis (NEC) (RR 0.2, 95% CI 0.02 to 1.3; one RCT, N = 75 infants; very low-quality evidence) between the prebiotic-supplemented group and the unsupplemented group. Duration of hospital stay was shorter in the prebiotic group than in the control group at a median (range) of 16 (9 to 45) days (95% CI 15.34 to 24.09) and 25 (11 to 80) days (95% CI 25.52 to 34.39), respectively. No other data were available for assessing effects of carbohydrate supplementation on short- and long-term growth, body mass index, body composition, and neurodevelopmental or cardio-metabolic outcomes.
AUTHORS' CONCLUSIONS: We found insufficient evidence on the short- and long-term effects of carbohydrate supplementation of human milk in preterm infants. The only trial included in this review presented very low-quality evidence, and study authors provided uncertain information about study methods and analysis. The evidence may be limited in its applicability because researchers included a small sample of preterm infants from a single centre. However, the outcomes assessed are common to all preterm infants, and this trial demonstrates the feasibility of prebiotic carbohydrate supplementation in upper-middle-income countries. Future trials should assess the safety and efficacy of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Although prebiotic carbohydrate supplementation in preterm infants is currently a topic of active research, we do not envisage that further trials of digestible carbohydrates will be conducted, as this is currently done as a component of multi-nutrient human milk fortification. Hence we do not plan to publish any further updates of this review.
早产儿出生时糖原储备低，需要更高的葡萄糖摄入量以达到胎儿生长速度。尽管母乳对早产儿有诸多益处，但可能无法充分满足这些快速生长婴儿的需求。在母乳中添加碳水化合物可能有所帮助。然而，关于添加碳水化合物对促进早产儿生长的益处或危害评估的数据较少。这是Cochrane系统评价的2018年更新版，该评价首次发表于1999年。
确定与未添加碳水化合物的母乳相比，添加碳水化合物的母乳喂养早产儿是否能改善生长、身体组成以及心脏代谢和神经发育结局，且无显著不良反应。
我们采用Cochrane新生儿评价组的标准检索策略，检索Cochrane对照试验中心注册库（CENTRAL；2017年第8期）、通过PubMed检索MEDLINE（1966年至2018年2月21日）、Embase（1980年至2018年2月21日）以及护理学与健康相关文献累积索引（CINAHL；1982年至2018年2月21日）。我们还检索了临床试验数据库、会议论文集以及检索到的文章的参考文献列表，以查找随机对照试验（RCT）和半随机试验。
已发表和未发表的对照试验符合纳入标准，若它们采用随机或半随机方法将住院接受母乳喂养的早产儿分配至添加或不添加额外碳水化合物的组。
两位综述作者独立提取数据，并使用推荐分级评估、制定与评价（GRADE）方法在结局层面评估试验质量和证据质量。我们计划对二分类数据使用风险比（RR），对连续数据使用均值差（MD）进行Meta分析，并给出各自的95%置信区间（CI）。我们计划使用固定效应模型，并通过敏感性分析探索异质性的潜在原因。我们联系研究作者获取更多信息。
一项未设盲的半随机对照试验（RCT）评估了75名早产儿中以益生元形式添加碳水化合物的母乳的效果，该试验符合纳入本综述的标准。我们确定了同一试验的两篇出版物，它们报告了关于设盲和随机化的不同方法。研究作者确认这些出版物涉及同一试验，但尚未阐明哪种方法正确。我们无法根据所呈现的数据重现分析。在30日龄时，试验中添加益生元碳水化合物组的早产儿平均体重高于未添加组（MD 160.4克，95%CI 12.4至308.4克；一项RCT，N = 75；极低质量证据）。我们未发现添加益生元组与未添加组在喂养不耐受风险（RR 0.64，95%CI 0.36至1.15；一项RCT，N = 75名婴儿；极低质量证据）或坏死性小肠结肠炎（NEC）（RR 0.2，95%CI 0.02至1.3；一项RCT，N = 75名婴儿；极低质量证据）方面有明显差异的证据。益生元组的住院时间中位数（范围）短于对照组，分别为16（9至45）天（95%CI 15.34至24.09）和25（11至80）天（95%CI 25.52至34.39）。没有其他数据可用于评估添加碳水化合物对短期和长期生长、体重指数、身体组成以及神经发育或心脏代谢结局的影响。
我们发现关于在早产儿母乳中添加碳水化合物的短期和长期影响的证据不足。本综述纳入的唯一试验提供了极低质量的证据，且研究作者提供的研究方法和分析信息不确定。由于研究人员纳入的是来自单一中心的少量早产儿样本，该证据的适用性可能有限。然而，所评估的结局对所有早产儿来说是常见的，并且该试验证明了在中高收入国家添加益生元碳水化合物的可行性。未来的试验应评估不同类型和浓度的碳水化合物添加对接受母乳喂养的早产儿的安全性和有效性。尽管目前早产儿添加益生元碳水化合物是一个活跃的研究课题，但我们预计不会再进行关于可消化碳水化合物的进一步试验，因为目前这是作为多营养素母乳强化的一个组成部分进行的。因此，我们不计划发布本综述的任何进一步更新。
