Early Exclusive Enteral Feeding in Preterm Infants: A Meta-Analysis

CONTEXT Early exclusive enteral feeding (EEF) in preterm infants may provide advantages such as improved nutritional delivery, reduced need for intravenous fluids (IVF), and lower health care costs. However, concerns persist regarding adverse outcomes, particularly necrotizing enterocolitis (NEC). OBJECTIVE To determine if EEF compared with progressive enteral feed (PEF) is associated with benefits without causing any adverse effects. DATA SOURCES MEDLINE, EMBASE, EMCARE, CINAHL, Cochrane Library, and clinical trial registries from inception to October 2025. STUDY SELECTION Randomized controlled trials comparing EEF commenced within 48 hours of birth with PEF in preterm infants. DATA EXTRACTION Two authors independently extracted data on clinical outcomes of interest using a standardized data collection form. RESULTS Eleven studies (n = 3145) were included (27+0 to 36+0 weeks). No significant differences were observed in the incidence of NEC stage 2 or greater (pooled relative risk [RR], 1.00; 95% CI, 1.00–1.01; P = .53), hypoglycemia (pooled RR, 1.00; 95% CI, 0.98–1.02; P = .80), or culture-proven sepsis (pooled RR, 1.03; 95% CI, 1.00–1.07; P = .08). EEF was associated with significantly shorter time to full feeds, reduced duration of IVF, faster regain of birth weight, and shorter hospital stay. Certainty of evidence (COE) was moderate for “any NEC” and low to very low for other outcomes. LIMITATIONS Presence of statistical heterogeneity in some outcomes and lack of blinding in interventions. CONCLUSIONS EEF appears to be feasible. Based on moderate COE, it does not appear to increase the risk of NEC. Larger and well-designed trials across diverse settings are needed to confirm its safety, evaluate potential benefits-including cost, and assess long-term outcomes.