A protocol for a systematic review and meta-analysis of the diagnostic accuracy of mid-regional pro-adrenomedullin in predicting invasive bacterial infection in children

BACKGROUND: The early recognition of invasive bacterial infections (IBI) in children can be difficult. Clinically it is often challenging to differentiate between the early stages of an IBI and a benign self-limiting viral infection. These challenges mandate a cautious approach resulting in the overuse of antimicrobial drugs with resultant antimicrobial resistance. Due to these challenges, there is growing research into the role of biomarkers for the early identification of children with IBI. Earlier and more accurate diagnoses may lead to improved clinical outcomes for children and reduced antimicrobial resistance. Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker that has been shown to be elevated in patients with IBI. The aim of this systematic review is to determine the diagnostic accuracy of MR-proADM at identifying children with IBI. METHODS: To identify relevant studies we will search MEDLINE, Embase, Web of Science and Scopus from 1980 to the present day for all human clinical trials involving children that report the test accuracy of MR-proADM. We will include case-control studies, cohort studies and randomised control trials reported in any language. In addition, we will hand-search reference lists and grey literature including conference abstracts and web searches. Two reviewers will independently screen study titles and abstracts for eligibility followed by full-text assessment and data extraction including population, setting, timing and use of index test and reference standard used. Methodological quality will be assessed, by two authors, according to the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2), any discrepancies will be resolved by a third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. DISCUSSION: This review will report the normal ranges for MR-proADM in health and the diagnostic accuracy of MR-proADM at identifying children with IBI. The review will help to define where in the diagnostic pathway MR-proADM could be useful including potential as a point-of-care test for children at first presentation with IBI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096295