PRISMA 2009 checklist.

<div> Background Predicting nontraumatic spontaneous intracerebral hemorrhage (SICH) patient prognosis has been commonly practiced, particularly when providing informed consent and considering surgical treatment. Biomarkers might provide more real-time evaluation of SICH patients’ condition than clinical prognostic scoring systems. This study aimed to evaluate the reliability of blood biomarkers in predicting prognosis in SICH patients by systematic review and meta-analysis. Methods Studies that evaluated the association of blood biomarker(s) with mortality and/or functional outcome in SICH patients up to October 11, 2024, were identified through PubMed, Google Scholars, Scopus databases, and reference lists. Studies that satisfied the inclusion criteria were included in the meta-analyses. Good functional outcome was defined by patient’s Glasgow Outcome Scale (GOS) ≥ 4 or modified Rankin scale mRS ≤ 2. Blood biomarkers were classified into the following categories: angiogenic factors, growth factors, inflammatory biomarkers, coagulation parameters, blood counts, and others. Individual meta-analysis was performed for every evaluation endpoint:7 days, 30 days, 3 months, 6 months, and 1 year. Meta-analyses were performed using Random Effect Mean-Difference with a 95% Confidence Interval for continuous data and visualized as forest plots in RevMan version 5.3 software. Cochrane Tool to Assess Risk of Bias in Cohort Studies was used to assess potential risk of bias of the included studies. GRADE Profiler was used to assess quality of evidence. Results Seventy-seven studies fulfilled the inclusion criteria. Surviving SICH patients have significantly lower C-reactive protein (CRP), D-dimer, copeptin, S100β, white blood cell (WBC), monocyte, and glucose than non-surviving patients. SICH patients with good functional outcome have lower D-dimer, Interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), WBC count, neutrophil count, monocyte count, copeptin and significantly higher lymphocyte counts and calcium levels. Out of all blood biomarkers that were evaluated, only S100β and copeptin had very high effect size and high certainty of evidence. Conclusion It is interesting to notice that many blood biomarkers significantly associated with SICH patients’ outcomes are related to inflammatory responses. This suggests that modulation of inflammation might be essential to improve SICH patients’ prognosis. We confidently concluded that S100β and copeptin are the most reliable blood biomarkers that can be used as prognosticators in SICH patients. On other biomarkers, in addition to heterogeneities and inconsistencies, several factors might affect the conclusions of current meta-analysis; thus, future studies to increase the certainties of evidence and effect size on other biomarkers are crucial. </div>