Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants

Background Early enteral feeding practices are potentiallymodifiable risk factors for necrotising enterocolitis in very pretermor very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of necrotising enterocolitis. However, slow feed advancement may delay establishment of full enteral feeding and be associated with metabolic and infectious morbidities secondary to prolonged exposure to parenteral nutrition. Objectives To determine the effect of slow rates of enteral feed advancement on the incidence of necrotising enterocolitis, mortality, and other morbidities in very preterm or VLBW infants. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group Specialised Register. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 8), MEDLINE, EMBASE, and CINAHL (to September 2014), conference proceedings, and previous reviews. Selection criteria Randomised or quasi- randomised controlled trials that assessed the effect of slow (up to 24 ml/kg per day) versus faster rates of advancement of enteral feed volumes upon the incidence of necrotising enterocolitis in very preterm or VLBW infants. Data collection and analysis Two review authors independently assessed trial eligibility and risk of bias and undertook data extraction. We analysed the treatment effects in the individual trials and reported the risk ratio and risk difference for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals. We used a fixed- effect model in meta- analyses and explored the potential causes of heterogeneity in sensitivity analyses. Main results We identified six randomised controlled trials in which a total of 618 infants participated. Most participants were stable preterm infants of birth weight between 1000 g and 1500 g. Few participants were extremely preterm, extremely low birth weight, or growth-restricted. The trials typically defined slow advancement as daily increments of 15 ml/kg to 20 ml/kg and faster advancement as 30 ml/kg to 35 ml/kg. Meta-analyses did not detect statistically significant effects on the risk of necrotising enterocolitis (typical risk ratio (RR) 0.96, 95% confidence interval (CI) 0.55 to 1.70) or all-cause mortality (typical RR 1.57, 95% CI 0.92 to 2.70). Infants who had slow advancement took significantly longer to regain birth weight (reported median differences 2 to 6 days) and to establish full enteral feeding (1 to 5 days). Authors' conclusions The available trial data suggest that advancing enteral feed volumes at daily increments of 30 ml/kg to 35 ml/kg does not increase the risk of necrotising enterocolitis in very preterm or VLBW infants. Advancing the volume of enteral feeds at slow rates resulted in several days delay in regaining birth weight and establishing full enteral feeds. The applicability of these findings to extremely preterm, extremely low birth weight, or growth-restricted infants is limited. Further randomised controlled trials in these populations may be warranted to resolve this uncertainty.