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.