Early versus Late Enteral Feeding in Preterm Intrauterine Growth Restricted Neonates with Antenatal Doppler Abnormalities: An Open-Label Randomized Trial

Background of the study: Enteral feeding in preterm neonates with intrauterine growth restriction (IUGR) and absent or reversed end diastolic flow (AREDF) on umbilical artery (UA) Doppler is delayed owing to an increased risk of necrotizing enterocolitis (NEC). Delaying enteral feeding with longer duration of parenteral nutrition (PN) carries an increased risk of sepsis. Objectives: To study early versus late feeding in preterm IUGR neonates for time required to attain sufficient feed volume to discontinue PN and increased risk of NEC or feed intolerance (FI). Design: Open-label randomized controlled trial. Setting: Tertiary care neonatal unit and fetal-maternal medicine unit in India. Participants: Preterm intrauterine growth restricted neonates' <= 32 weeks with AREDF on UA Doppler enrolled from 1 January 2014 to 31 July 2015. Intervention: Randomized to receive early or late feeding using mothers own or donor breast milk as per a feed initiation and advancement protocol. Primary outcome: Time in days required to attain sufficient feed volume allowing discontinuation of PN and incidence of NEC in neonates fed early versus late. Results: There were 77 eligible neonates. Sixty-two neonates were included and stratified as extreme preterm (27-29 weeks) (n = 20) and very preterm (30-32 weeks) (n = 42). Ten extreme preterm and 21 very preterm neonates were randomized to each early feeding and late feeding arm. There was a significantly faster attainment of sufficient feeds in the early feeding arm of both the stratified groups [extreme preterm: median 14 days (Interquartile range IQR: 12-15) compared with 18 days (IQR: 18-20), hazard ratio (HR): 1.59, 95% CI: 0.626-4.078; very preterm: 12 days (IQR: 10-14) as compared with 16 days (IQR 15-17), HR: 1.89, 95% CI: 1.011-3.555]. There was no difference in the incidence of NEC, FI and combined outcome of NEC and FI. Conclusion: Early feeding in preterm IUGR neonates with AREDF on antenatal UA Doppler allowed earlier discontinuation of PN, allowing birth weight to be regained earlier and did not increase the incidence of NEC and FI.