Review question
We reviewed the evidence to determine whether addition of extra fat (supplements) to human milk fed to infants born early (preterm) compared with no additional fat improves growth, body fat, obesity, heart problems, high blood sugar, and brain development, without significant side effects.
Background
Preterm babies at birth lack adequate fat stores because they are born before laying down nutrient stores in the rapid growth phase of the third trimester of pregnancy. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Fat provides approximately half of the calories in human milk and supports growth and brain development. Although human milk has many benefits for the preterm baby, it may contain variable and insufficient quantities of fat for adequate growth and development. Inadequate supply of fat in preterm infants fed human milk may adversely affect their growth and development. Therefore, additional fat may be added to human milk, usually by adding commercially prepared fat mixtures to a small amount (e.g. 20 mL) of expressed breast milk.
Study characteristics
We included one trial with very low-quality evidence and involving 14 preterm infants. The search is up to date as of August 2019.
Key results
Addition of extra fat to human milk for preterm infants showed no clear benefits with regards to short-term rates of weight gain, length gain, and head growth. There was no evidence that the extra fat increased the risk of feeding intolerance. No data were available regarding the effects of addition of extra fat on long-term growth, body fat, obesity, high blood sugar, or brain development. There were also limited data to assess side effects.
Conclusions
There was insufficient high-quality evidence on the benefits and harms of the addition of extra fat to human milk in preterm infants, and no long-term outcomes have been reported. Since addition of extra fat to human milk is currently done as part of multi-nutrient fortification, future trials should evaluate the effect of the fat component on short- and long-term growth, body fat, obesity, high blood sugar, or brain development. The right amount and composition of extra fat needed, side effects, and delivery practices should also be evaluated.
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 growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers.
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 2020 update of a Cochrane Review last published in 2000.
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.
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 23 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
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.
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.
One randomised trial involving 14 preterm infants was included. This risk of bias was unclear for all methodological domains. Very low-quality evidence means that there is uncertainty about the effect of fat supplemention on 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,), length (MD 0.1 cm/week, 95% CI −0.08 to 0.3; 1 RCT, n = 14 infants) and head circumference (MD 0.2 cm/week, 95% CI −0.07 to 0.4; 1 RCT n = 14 infants), and on the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants). No data were available regarding the effects of fat supplementation on the risk of necrotising enterocolitis or neurodevelopmental outcomes.