title: Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants.
abstract: BACKGROUND
  Early enteral feeding practices are potentially modifiable risk factors for necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Observational studies suggest that conservative feeding regimens, including slowly advancing enteral feed volumes, reduce the risk of NEC. 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.
  
  
  OBJECTIVE
  To determine the effect of slow rates of enteral feed advancement on the incidence of NEC, mortality, and other morbidities in very preterm or VLBW infants.
  
  
  METHODS
  We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE via PubMed (1966 to August 2015), EMBASE (1980 to August 2015), and CINAHL (1982 to August 2015). We also searched clinical trials databases, conference proceedings, previous reviews, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
  
  
  METHODS
  Randomised or quasi-randomised controlled trials that assessed the effect of slow (up to 24 mL/kg/day) versus faster rates of advancement of enteral feed volumes upon the incidence of NEC in very preterm or VLBW infants.
  
  
  METHODS
  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 (RR) and risk difference (RD) for dichotomous data and mean difference for continuous data, with respective 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses.
  
  
  RESULTS
  We identified nine randomised controlled trials in which 949 infants participated. Most participants were stable preterm infants with birth weights between 1000 and 1500 g. Fewer participants were extremely preterm, extremely low birth weight, or growth-restricted. The trials typically defined slow advancement as daily increments of 15 to 24 mL/kg and faster advancement as 30 to 40 mL/kg. Meta-analyses did not show statistically significant effects on the risk of NEC (typical RR 1.02, 95% CI 0.64 to 1.62; typical RD -0.00, 95% CI -0.03 to 0.03) or all-cause mortality (typical RR 1.18, 95% CI 0.90 to 1.53; typical RD 0.03, 95% CI -0.02 to 0.08). Slow feeds advancement delayed the establishment of full enteral nutrition by one to five days and increased the risk of invasive infection (typical RR 1.46, 95% CI 1.03 to 2.06; typical RD 0.07, 95% CI 0.01 to 0.13; number needed to treat for an additional harmful outcome 14, 95% CI 8 to 100).
  
  
  CONCLUSIONS
  The available trial data suggest that advancing enteral feed volumes at daily increments of 30 to 40 mL/kg (compared to 15 to 24 mL/kg) does not increase the risk of NEC or death in VLBW infants. Advancing the volume of enteral feeds at slow rates results in several days of delay in establishing full enteral feeds and increases the risk of invasive infection. 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.
authors.affiliation: Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, UK, Y010 5DD.
authors.forename: Jessie
authors.initials: J
authors.lastname: Morgan
authors.forename: Lauren
authors.initials: L
authors.lastname: Young
authors.forename: William
authors.initials: W
authors.lastname: McGuire
mesh_terms: D004750:Enteral Nutrition / Q000009:adverse effects / Q000379:methods*; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000209:etiology / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D010288:Parenteral Nutrition / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic