Does addition of extra carbohydrate to human milk fed to preterm infants compared with no additional carbohydrate improve growth, body fat, obesity, heart problems, high blood sugar, and brain development without causing significant side effects?
Not enough carbohydrate intake in preterm infants may result in poor growth and development. Breast milk is the best food for preterm infants, but feeding them only breast milk may be nutritionally inadequate. Adding carbohydrate to breast milk may help. However, not enough data can be found on assessing the benefits and harms of adding carbohydrate to breast milk to promote growth in preterm infants.
We found one trial involving 75 preterm infants with very low-quality evidence on the effects of adding extra prebiotics (a type of carbohydrate) to human milk in preterm infants. A second publication by the same study authors reported different methods regarding blinding and randomisation of the trial. Study authors confirmed that these publications describe the same trial but have not yet clarified which method is accurate. We were unable to reproduce the analyses from the data presented. The search is up to date as of August 2019.
Prebiotic carbohydrate supplementation increased the mean weight of preterm infants at day 30 and resulted in a shorter hospital stay compared with control. No evidence shows a clear difference in risk of feeding intolerance or necrotising enterocolitis between the prebiotic-supplemented and unsupplemented groups. No other data were available to show the effects of adding extra carbohydrate to human milk on short- and long-term growth, body fat, obesity, brain development, and heart problems.
Evidence on the short- and long-term effects of adding extra carbohydrate to human milk in preterm infants is lacking. This systematic review found very low-quality evidence on the effects of adding prebiotic carbohydrate to human milk in preterm infants, along with uncertainties about methods and analysis. The single trial included a small sample of Iranian preterm infants, and so the evidence may be considered as not generalisable. However, the outcomes assessed are common to all preterm infants, and the trial shows that adding prebiotic carbohydrate to human milk is possible in developing countries. Further research is needed to assess the benefits and harms of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Currently, digestible carbohydrate supplementation in preterm infants is provided as a component of multi-nutrient human milk fortification. Hence we do not plan to publish further updates of this review.
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.
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 2020 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 Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 22 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 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.