The utility of base excess in neonatal sepsis: A systematic review and meta-analysis

Background: Sepsis remains a significant cause of neonatal mortality and morbidity. Early diagnosis remains challenging due to nonspecific clinical presentation and limitations of current diagnostic approaches. Base excess (BE), derived from routine blood gas analysis, has emerged as a potential rapid biomarker reflecting metabolic disturbances associated with sepsis. We aim to evaluate the diagnostic and prognostic utility of BE in neonatal sepsis. Methods: A literature search was conducted across PubMed/MedLine, Scopus, Cochrane Library, EBSCOHost, and gray literature repositories from inception to July 2025. We included studies reporting BE measurement in neonatal sepsis. Two-by-two data were pooled using bivariate random-effects models to estimate sensitivity, specificity, and area under the curve (AUC). Mortality risk was assessed using odds ratios. This study followed the PRISMA guideline, and evidence certainty was evaluated using the GRADE methodology. The protocol has been registered in the PROSPERO (CRD42024601108). Results: Six studies were included in this meta-analysis. BE threshold ≤−5 mEq/L from arterial/capillary blood demonstrated a pooled sensitivity of 85.8% (95% CI: 59.9%–96.1%), a specificity of 82.9% (95% CI: 46.2%–96.5%), and an AUC of 0.909. Cord blood BE ≤ −10 mEq/L showed high specificity (96.7%, 95% CI: 91.5%–98.8%) but low sensitivity (10.3%, 95% CI: 6.5%–15.7%). Decreased BE levels were associated with increased mortality risk (OR 3.14; 95% CI: 1.34-7.36). The certainty of evidence was low. Conclusion: BE shows potential as a biomarker for neonatal sepsis. However, the low-certainty evidence underscores the need for further prospective validation and exploration of BE’s role within combined biomarker algorithms before widespread clinical implementation.