早産児の成長を促進するための母乳の脂肪分補充
Abstract
Background
As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2018 update of a Cochrane Review last published in 2000.
Objectives
To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio‐metabolic, and neurodevelopmental outcomes without significant adverse effects.
Search methods
We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 1), MEDLINE via PubMed (1966 to 08 February 2018), Embase (1980 to 08 February 2018), and CINAHL (1982 to 08 February 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi‐randomised trials.
Selection criteria
Published and unpublished randomised controlled trials were eligible if they used random or quasi‐random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat.
Data collection and analysis
No new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta‐analyses using risk ratio (RR) for dichotomous data and mean difference (MD) 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.
Main results
One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat‐supplemented and unsupplemented groups in in‐hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI −2.4 to 3.6; 1 RCT, n = 14 infants, very low‐quality evidence), length (MD 0.1 cm/week, 95% CI −0.08 to 0.3; 1 RCT, n = 14 infants, very low‐quality evidence) and head circumference (MD 0.2 cm/week, 95% CI −0.07 to 0.4; 1 RCT n = 14 infants, very low‐quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low‐quality evidence). No data were available regarding the effects of fat supplementation on long‐term growth, body mass index, body composition, neurodevelopmental, or cardio‐metabolic outcomes.
Authors' conclusions
The one included trial suggests no evidence of an effect of fat supplementation of human milk on short‐term growth and feeding intolerance in preterm infants. However, the very low‐quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long‐term outcomes were reported. Further high‐quality research should evaluate the effect on short and long‐term growth, neurodevelopmental and cardio‐metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.
PICO
Plain language summary
早産児の成長を促進するための母乳の脂肪分補充
レビューの論点
早期産児に与える母乳に脂肪分を添加（補充）した場合、添加しない場合と比較して、大きな副作用を生じることなく、発育、体脂肪、肥満、心疾患、高血糖および脳の発達を改善するかどうかに関するエビデンスのレビューを実施した。
背景
早期産児は急速な発育がみられる時期である妊娠第3期に、栄養分を蓄える前に生まれてくるため、出生時の脂肪蓄積量が不足している。このため、早期産児が十分に成長・発達するためには、正期産児と比較してより多くの脂肪分を摂取する必要がある。脂肪は母乳のカロリーの約半分を占め、乳児の発育や脳の発達に役立っている。母乳は早期産児にとって多数のメリットがあるが、成長や発達に必要な脂肪の含有量にばらつきがあり、十分な量が含まれていない場合がある。早期産児に脂肪分の少ない母乳を与えると、発育や発達に悪影響を及ぼす可能性がある。このため、母乳に脂肪分を添加することがある。通常は市販の脂質添加剤を少量（例：20 mL）の母乳に混ぜる。
試験の特性
早期産児14児を対象とした、エビデンスの質が極めて低い1件の試験をレビューに組み入れた。この検索結果は2018年2月時点のものである。
主要な結果
早期産児に与える母乳に脂肪分を添加した結果、短期間における体重や身長の増加割合、および頭部の成長に明らかな有用性は認められなかった。脂肪添加によってfeeding intolerance のリスクが上昇するというエビデンスは確認されなかった。脂肪添加が成長、体脂肪、肥満、高血糖および脳の発達に及ぼす長期的な影響に関するデータは入手できなかった。また、副作用を評価するにはデータが不足していた。
結論
早期産児に与える母乳に脂肪分を添加した場合の有益性および有害性に関する質の高いエビデンスが不足しており、長期転帰も報告されていない。現在、母乳への脂肪添加は栄養強化の一環として実施されているため、今後の試験では、成長、体脂肪、肥満、高血糖および脳の発達に対する脂質成分の短期的および長期的な効果について評価すべきである。適正な脂肪添加量、組成、副作用および投与方法についても評価すべきである。
