Early full or near-full enteral feeding in clinically stable preterm infants across healthcare settings: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Preterm infants are at high risk of feeding intolerance. Early full enteral feeding (EFEF) may promote gastrointestinal maturation and reduce hospital stay, but concerns exist about its generalizability across different healthcare contexts. METHODS: We systematically searched multiple databases and included nine randomized controlled trials comparing early full enteral feeding (EFEF), defined as initiation of full enteral feeding immediately after birth without parenteral nutrition or fluid supplementation, with gradual feeding strategies in preterm infants. Subgroup analyses were performed according to healthcare settings (high-income vs. low- and middle-income countries). The primary outcome was length of hospital stay. RESULTS: Nine randomized controlled trials involving 2,777 infants were included. EFEF reduced length of hospital stay (MD = -4.41 days, 95% CI: -7.05 to -1.76), time to regain birth weight (MD = -2.29 days, 95% CI: -3.66 to -0.91), and time to achieve full enteral feeding (MD = -1.58 days, 95% CI: -2.32 to -0.84). No statistically significant difference was observed in feeding intolerance (RR = 0.78, 95% CI: 0.49-1.22), necrotizing enterocolitis (RR = 0.89, 95% CI: 0.38-2.09), invasive infection (RR = 0.82, 95% CI: 0.43-1.57), mortality (RR = 1.08, 95% CI: 0.55-2.09), or hypoglycaemia (RR = 1.53, 95% CI: 0.42-5.59), although the confidence intervals for serious adverse outcomes were wide. Subgroup analyses showed no statistically significant interaction between healthcare settings for either length of hospital stay (P for interaction = 0.79) or mortality (P for interaction = 0.90). CONCLUSIONS: EFEF may shorten hospital stay and accelerate feeding-related milestones in clinically stable preterm infants. However, the certainty of evidence was low to very low, and estimates for serious adverse outcomes were imprecise. The current evidence therefore does not establish the safety of EFEF or determine whether its effects differ across healthcare settings.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251251351.