What does this research mean for the field?

Elevated serum levels of specific biomarkers, including IL-6, IL-8, Neuron Specific Enolase (NSE), and TNF-α, are significantly associated with adverse long-term outcomes in Neonatal Encephalopathy. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to evaluate serum biomarkers for predicting outcomes in neonatal encephalopathy.

May 30, 2026Open Access

Neonatal Encephalopathy biomarkers: outcome prediction from blood samples: systematic review and meta-analysis

MOMary O'DeaTrinity College Dublin THTim HurleyTrinity College ABAoife BranaganTrinity College

Key Points

The aim is to evaluate serum biomarkers for predicting outcomes in neonatal encephalopathy.
Systematic review and meta-analysis of studies on biomarkers in neonatal encephalopathy, registered with PROSPERO.
Literature search across multiple databases yielding 98 eligible studies for analysis.
Calculated mean differences in biomarkers for normal vs adverse outcomes based on findings from 47 included studies.
Higher levels of IL-6 (70.22 pg/ml), IL-8 (15.72 pg/ml), NSE (38.95 pg/ml), and TNF-α (20.84 pg/ml) correlate with adverse long-term outcomes in neonatal encephalopathy.
Elevated IL-6 (22.57 pg/ml) and lactate (4.5 mg/dL) indicate increased risk for adverse short-term outcomes.
Lack of uniformity in timing and analysis of biomarkers limits clear conclusions.

Abstract

Abstract Background Biomarkers are important for early diagnosis, guiding prognosis, and identifying potential therapeutic agents. Many biomarkers have been investigated as potential prognostic markers in Neonatal Encephalopathy (NE), none are measured routinely. We examined current evidence of serum biomarkers to predict outcome. Methods We prospectively registered with PROSPERO. We searched EMBASE, PubMed, World of Science, and the Cochrane Library databases for studies of biomarkers in NE. We dichotomised participants by normal or adverse outcome and calculated the mean difference (MD) in biomarkers between groups. Results Literature search provided 3046 results. 98 studies of >20 different biomarkers were eligible. We completed meta-analyses, including 47 studies, for serum interleukin (IL)-1β, IL-6, IL-8, IL-10, Neuron Specific Enolase (NSE), S100, and Tumour Necrosis Factor (TNF)-α. Higher IL-6 70.22 pg/ml (95% confidence interval (CI) 0.55, 139.89), IL-8 15.72 pg/ml (95% CI 3.59, 27.85), NSE 38.95 pg/ml (95% CI 18.33, 59.57), and TNF-α 20.84 pg/ml (95% CI 6.24, 35.45) were associated with adverse long-term outcome. Higher IL-6 22.57 pg/ml (95% CI 0.66, 44.49) and lactate 4.5 mg/dL (95% CI 0.66, 44.49) were associated with adverse short-term outcomes. Conclusion Several biomarkers especially provide promising prognostic value in NE. Greater uniformity in biomarker outcome reporting would allow improved evidence synthesis. Impact Statement Elevated biomarkers such as Serum IL-6, IL-8, NSE, and TNF-α were associated with adverse long-term outcomes in NE and are promising as surrogate biomarkers of early outcomes Small sample size, lack of uniformity of timing and sampling, as well as analysis, make definitive conclusions challenging. Future collaboration to standardise timing and analysis of biomarkers in larger international cohorts would facilitate translation to the bedside.

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