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

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, it is unclear whether slow feed advancement may delay establishment of full enteral feeding, and if it could be associated with infectious morbidities secondary to prolonged exposure to parenteral nutrition. Objectives To determine the effects of slow rates of enteral feed advancement on the risk of NEC, mortality, and other morbidities in very preterm or VLBW infants. Search methods We searched CENTRAL (2020, Issue 10), Ovid MEDLINE (1946 to October 2020), Embase via Ovid (1974 to October 2020), Maternity and Infant Care database (MIDIRS) (1971 to October 2020), CINAHL (1982 to October 2020), and clinical trials databases and reference lists of retrieved articles for eligible trials. Selection criteria We included randomised or quasi-randomised controlled trials that assessed effects of slow (up to 24 mL/kg/d) versus faster rates of advancement of enteral feed volumes on the risk INK in very preterm or VLBW infants. Data collection and analysis Two review authors separately evaluated trial risk of bias, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence. Outcomes of interest were NEC, all-cause mortality, feed intolerance, and invasive infection. Main results We included 14 trials involving a total of 4033 infants (2804 infants participated in one large trial). None of the trials masked parents, caregivers, or investigators. Risk of bias was otherwise low. Most infants were stable very preterm or VLBW infants of birth weight appropriate for gestation. About one-third of all infants were extremely preterm or extremely low birth weight (ELBVV), and about one fifth were small for gestational age, growth-restricted, or compromised as indicated by absent or reversed end-diastolic flow velocity in the foetal umbilical artery. Trials typically defined slow advancement as daily increments of 15 to 24 mL/kg, and faster advancement as daily increments of 30 to 40 mL/kg. Meta-analyses showed that slow advancement of enteral feed volumes probably has little or no effect on the risk of NEC (RR 1.06, 950/o confidence interval (CI) 0.83 to 1.37; RD 0.00, 95% C1-0.01 to 0.02; 14 trials, 4026 infants; moderate-certainty evidence) or all-cause mortality prior to hospital discharge (RR 1.13, 95% CI 0.91 to 1.39; RD 0.01, 95% CI 0.01 to 0.02; 13 trials, 3860 infants; moderate-certainty evidence). Meta-analyses suggested that slow advancement may slightly increase feed intolerance (RR 1.18, 95% CI 0.95 to 1.46; RD 0.05, 95% CI 0.02 to 0.12; 9 trials, 719 infants; low-certainty evidence) and may slightly increase the risk of invasive infection (RR 1.14, 95% CI 0.99 to 1.31; RD 0.02, 95% CI 0.00 to 0.05; 11 trials, 3583 infants; low-certainty evidence). Authors' conclusions The available trial data indicate that advancing enteral feed volumes slowly (daily increments up to 24 mL/kg) compared with faster rates probably does not reduce the risk of NEC, death, or feed intolerance in very preterm or VLBW infants. Advancing the volume of enteral feeds at a slow rate may slightly increase the risk of invasive infection.