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Neonatal Encephalopathy biomarkers: outcome prediction from blood samples: systematic review and meta-analysis
Mary O'Dea1,2,3,4,5, Tim Hurley1,2,3,6, Aoife Branagan1,2,3,4,6
1Discipline of Paediatrics and Child Health, Trinity College, the University of Dublin, Dublin, Ireland.
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.
