Enteral Feeding Strategies in Preterm Neonates ≤32 weeks Gestational Age: A Systematic Review and Network Meta-Analysis

Introduction:
Critical aspects of time of feed initiation, advancement, and volume of feed increment in preterm neonates remain largely unanswered.

Methods:
Medline , Embase, CENTRAL and CINAHL were searched from inception until 25th September 2020. Network meta-analysis with the Bayesian approach was used. Randomized controlled trials (RCTs) evaluating preterm neonates ≤32 weeks were included. Feeding regimens were divided based on the following categories: initiation day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); advancement day: early (<72 h), moderately early (72 h–7 days), and late (>7 days); increment volume: small volume (SV) (<20 mL/kg/day), moderate volume (MoV) (20–< 30 mL/kg/day), and large volume (≥30 mL/kg/day); and full enteral feeding from the first day. Sixteen regimens were evaluated. Combined outcome of necrotizing enterocolitis (NEC) stage ≥ II or mortality before discharge was the primary outcome.

Results:
A total of 39 studies enrolled around 6,982 neonates. Early initiation (EI) with moderately early or late advancement using MoV increment enteral feeding regimens appeared to be most efficacious in decreasing the risk of NEC or mortality when compared to EI and early advancement with SV increment (risk ratio [95% credible interval]: 0.39 [0.12, 0.95]; 0.34 [0.10, 0.86]) (GRADE–very low).

Conclusions:
Early initiated, moderately early, or late advanced with MoV increment feeding regimens might be most appropriate in decreasing the risk of NEC stage ≥II or mortality. In view of the certainty of evidence being very low, adequately powered RCTs evaluating these 2 strategies are warranted.