Systematic review and meta-analysis of the diagnostic value of four biomarkers in detecting neonatal sepsis in low- and middle-income countries.

BACKGROUND: Biomarkers may enhance diagnostic capability for common paediatric infections, especially in low- and middle-income countries (LMICs) where standard diagnostic modalities are frequently unavailable, but disease burden is high. A comprehensive understanding of the diagnostic capability of commonly available biomarkers for neonatal sepsis in LMICs is lacking. Our objective was to systematically review evidence on biomarkers to understand their diagnostic performance for neonatal sepsis in LMICs. METHODS: We conducted a systematic review and meta-analysis of studies published in English, Spanish, French, German, Dutch, and Arabic reporting the diagnostic performance of C reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and procalcitonin (PCT) for neonatal sepsis. We calculated pooled test characteristics and the area under the curve (AUC) for each biomarker compared with the reference standards blood culture or clinical sepsis defined by each article. RESULTS: Of 6570 studies related to biomarkers in children, 134 met inclusion criteria and included 23 179 neonates. There were 80 (59.7%) studies conducted in LMICs. CRP of ≥60 mg/L (AUC 0.87, 95% CI 0.76 to 0.91) among 1339 neonates and PCT of ≥0.5 ng/mL (AUC 0.87, 95% CI 0.70 to 0.92) among 617 neonates demonstrated the greatest discriminatory value for the diagnosis of neonatal sepsis using blood culture as the reference standard in LMICs. CONCLUSIONS: PCT and CRP had good discriminatory value for neonatal sepsis in LMICs. ESR and WBC demonstrated poor discrimination for neonatal sepsis in LMICs. Future studies may incorporate biomarkers into clinical evaluation in LMICs to diagnose neonatal sepsis more accurately. PROSPERO REGISTRATION NUMBER: CRD42020188680.

Metabolomics profiling in acute liver transplant rejection in a pediatric population.

Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p < 0.05) showed bile acid biosynthesis and tryptophan metabolism as the top two differentiating pathways. Network analysis also identified tryptophan and clustered with liver enzymes and steroid use. We conclude metabolic profiling of plasma from children with acute liver transplant rejection demonstrates > 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.