Cord blood biomarkers in infants with neonatal encephalopathy: a systematic review and meta-analysis

IMPORTANCE: Cord blood biomarkers could aid in the early diagnosis of neonatal encephalopathy (NE) and detect neonates likely to benefit from interventions. METHODS: A systematic review and meta-analysis were conducted. PubMed, Scopus, OVID MEDLINE, Embase, and Cochrane were searched through July 2024. Eligible studies were prospective, retrospective, longitudinal, or cross-sectional in English. Reviews, case series, case-control, and opinion articles were excluded. Standardized mean differences were calculated with random-effects models; heterogeneity was assessed with I² and bias with Egger's test. RESULTS: Of 1705 studies screened, 63 were reviewed and 49 meta-analyzed, covering 51 cord blood biomarkers, metabolomic profiles, and microRNA/mRNA expression profiles. Several biomarkers were significantly elevated in neonates with NE compared to controls, including tumor necrosis factor-alpha (3.34; 95%CI 2.52-4.15), prooxidant-antioxidant balance (0.80; 95%CI 0.59-1.00), activin-A (0.88; 95%CI 0.52-1.24), troponin (6.13; 95%CI 3.33-8.93), S100 calcium-binding protein B (2.74; 95%CI 0.94-4.54), glial fibrillary acidic protein, neuron-specific enolase, tau, neurofilament light protein, interleukin-6, interleukin-1, malondialdehyde, hypoxanthine, and nucleated red blood cells. Metabolomic changes and altered miRNA expression were also reported. CONCLUSIONS: Early detection of specific cord blood biomarkers shows promise for NE diagnosis. Further prospective studies are needed to validate biomarker panels for clinical use. IMPACT: Early detection of specific cord blood biomarkers may help identifying neonates with neonatal encephalopathy (NE). Tumor necrosis factor-alpha (TNF-α), prooxidant-antioxidant balance, nucleated red blood cells, and activin-A were significantly elevated in neonates with NE compared to controls. S100 calcium-binding protein B (S100B) and IL-6 were higher in neonates with moderate/severe NE compared to neonates with mild NE. TNF-α, prooxidant-antioxidant balance, nucleated red blood cells, activin-A, S100B, and IL-6 are the most promising cord blood biomarkers for early diagnosis and disease severity assessment of NE.