Background: Neonatal invasive candidiasis (NIC) is a leading cause of infection-related morbidity and mortality in preterm neonates. Several studies have shown that (1,3)-Beta-D-Glucan (BDG) was accurate in detecting invasive fungal infection in adults, but studies in neonates are scarce. Objectives: To obtain summary estimates of the accuracy of BDG detection in serum for the diagnosis of NIC. Data sources: We searched Medline, Embase, Clinicaltrials.gov, and Google Scholar (inception to July 2019). We checked the reference lists of included studies, clinical guidelines, and review articles. Study eligibility criteria: We included studies that assessed the accuracy of BDG against a reference standard that defined groups of patients with ordinal levels of NIC probability (e.g., proven, probable, possible) and included fungal blood culture. Participants: Neonates suspected of having NIC. Interventions: BDG measurement in serum (Fungitell® assay). Methods: We assessed risk of bias and applicability using QUADAS-2. We used bivariate meta-analysis to produce summary estimates of diagnostic accuracy at prespecified positivity thresholds of 80 and 120 pg/ml. This study was registered with PROSPERO (CRD42018089545). Results: We included eight studies (465 participants). Of these, two were judged at low overall risk of bias. There was substantial variability across studies in the reference standards used. At a positivity threshold of 80 pg/ml, summary estimates of sensitivity and specificity of BDG were 89% (95% CI: 80%-94%) and 60% (53%-66%), respectively; summary sensitivity for detecting proven cases of NIC was 99% (93%-100%). At a positivity threshold of 120 pg/ml, summary estimates of sensitivity and specificity were 81% (71%-88%) and 80% (67%-88%), respectively. Conclusions: Because of high sensitivity, BDG seems promising to rule-out NIC. It might be too early to recommend its use because of the scarcity of reliable clinical data, heterogeneity in case definitions, and unstable accuracy estimates. Abbreviations BDG: (1,3)-Beta-D-Glucan CRP: C-reactive protein NIC: Neonatal invasive candidiasis
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