High versus standard volume enteral feeds to promote growth in preterm or low birth weight infants

Thangaraj Abiramalatha, Niranjan Thomas, Vijay Gupta, Anand Viswanathan, William McGuire

Breast milk alone, given at standard recommended volumes (150 to 180 mL/kg/d), is not adequate to meet the protein, energy, and other nutrient requirements of growing preterm or low birth weight infants. One strategy that may be used to address these potential nutrient deficits is to give infants enteral feeds in excess of 200 mL/kg/d ('high-volume' feeds). This approach may increase nutrient uptake and growth rates, but concerns include that high-volume enteral feeds may cause feed intolerance, gastro-oesophageal reflux, aspiration pneumonia, necrotising enterocolitis, or complications related to fluid overload, including patent ductus arteriosus and bronchopulmonary dysplasia. To assess the effect on growth and safety of feeding preterm or low birth weight infants with high (> 200 mL/kg/d) versus standard (≤ 200 mL/kg/d) volume of enteral feeds. Infants in intervention and control groups should have received the same type of milk (breast milk, formula, or both), the same fortification or micronutrient supplements, and the same enteral feeding regimen (bolus, continuous) and rate of feed volume advancement.To conduct subgroup analyses based on type of milk (breast milk vs formula), gestational age or birth weight category of included infants (very preterm or VLBW vs preterm or LBW), presence of intrauterine growth restriction (using birth weight relative to the reference population as a surrogate), and income level of the country in which the trial was conducted (low or middle income vs high income) (see 'Subgroup analysis and investigation of heterogeneity'). We used the Cochrane Neonatal standard search strategy, which included searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2) in the Cochrane Library; MEDLINE (1946 to November 2016); Embase (1974 to November 2016); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to November 2016), as well as conference proceedings, previous reviews, and trial registries. Randomised and quasi-randomised controlled trials that compared high-volume versus standard-volume enteral feeds for preterm or low birth weight infants. Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported the risk ratio and risk difference for dichotomous data, and the mean difference for continuous data, with respective 95% confidence intervals. . We assessed the quality of evidence at the outcome level via the GRADE approach. We found one eligible trial that included 64 infants. This trial was not blinded. Analysis showed a higher rate of weight gain in the high-volume feeds group: mean difference 6.20 g/kg/d (95% confidence interval 2.71 to 9.69). There was no increase in the risk of feed intolerance or necrotising enterocolitis with high-volume feeds, but 95% confidence intervals around these estimates were wide. We assessed the quality of evidence for these outcomes as 'low' or 'very low' because of imprecision of the estimates of effect and concern about risk of bias due to lack of blinding in the included trial. Trial authors provided no data on other outcomes, including gastro-oesophageal reflux, aspiration pneumonia, necrotising enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, or long-term growth and neurodevelopment. We found only very limited data from one small unblinded trial on the effects of high-volume feeds on important outcomes for preterm or low birth weight infants. The quality of evidence is low to very low. Hence, available evidence is insufficient to support or refute high-volume enteral feeds in preterm or low birth weight infants. A large, pragmatic randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice.