**Background:** Acute pancreatitis (AP) is a potentially severe inflammatory condition with mortality rates of 20-30% in severe cases. Nutritional support is critical, and enteral nutrition (EN) is preferred over parenteral nutrition due to better preservation of intestinal mucosal function and lower infection risk. However, the optimal timing for initiating EN—early versus delayed—remains debated. This systematic review and meta-analysis aimed to compare complications and hospital stay between early enteral nutrition (EEN) and delayed enteral nutrition (DEN) in patients with AP.
**Methods:** The authors searched PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar up to December 1, 2022. Studies were included if they involved patients diagnosed with AP, all received EN, and were divided into EEN and DEN groups based on EN initiation time. Exclusion criteria included no AP patients, no EEN vs. DEN comparison, reviews/comments/case reports, and non-English publications. Two independent investigators screened studies, assessed quality using the Newcastle-Ottawa Quality Assessment Scale (NOS), and extracted data. Statistical analysis used relative risk (RR) for categorical variables and standard mean difference (SMD) for continuous variables, with 95% confidence intervals. Heterogeneity was assessed using I² and χ² tests; fixed-effect models were used when I²<50%, random-effects models otherwise. Meta-regression explored sources of heterogeneity. Publication bias was evaluated using funnel plots and Egger's test.
**Key Results:** From 1,212 identified studies, 17 studies (15 RCTs, 2 retrospective) with 1,637 patients (831 EEN, 806 DEN) were included. Publication years ranged from 1997-2017, with recruitment from 1990-2016. Most studies were high quality (NOS score >7). EEN initiation cutoffs were <24 h (3 studies), <48 h (9 studies), and <72 h (5 studies).
- **Mortality:** DEN group had significantly higher mortality (RR=1.95; 95% CI, 1.21-3.14; P=0.006; I²=0.8%; 9 studies).
- **Sepsis:** DEN group had significantly higher risk of sepsis (RR=2.82; 95% CI, 1.10-7.18; P=0.03; I²=0%; fixed effect).
- **Necrotic collection:** No significant difference (RR=1.074; P>0.05).
- **Walled-off pancreatic necrosis:** No significant difference (RR=1.342; P>0.05).
- **ARDS, MODS, SIRS:** No significant differences (RR=1.01, 1.27, and 1.07, respectively; all P>0.05).
- **Hospital stay:** Significantly shorter in EEN group (median 17.4 vs. 20.0 days; SMD=-0.93; 95% CI, -1.57 to -0.29; P<0.001; I²=90.4%; random-effects model).
- **Subgroup analysis by cutoff time:** At <48 h cutoff, DEN was associated with a 3.89-fold increase in mortality risk (95% CI, 1.25-12.17; P=0.019). No significant differences were found for other complications at any cutoff.
- **Meta-regression:** Only severity of AP significantly impacted hospital stay heterogeneity (Coefficient=0.903; P=0.025).
- **Publication bias:** Egger's test and funnel plots showed no significant publication bias for any outcome.
**Clinical Implications:** This meta-analysis provides evidence that early enteral nutrition reduces mortality, sepsis risk, and hospital stay in patients with acute pancreatitis. The 48-hour cutoff appears particularly beneficial for mortality reduction. These findings support current guidelines recommending EN initiation within 24-72 hours of admission. However, the optimal timing remains debated, and heterogeneity in hospital stay data warrants further investigation. Clinicians should consider initiating EN as early as feasible, ideally within 48 hours, in patients with AP who can tolerate enteral feeding.