Metabolomics in neonatal sepsis

Abstract

<p>BACKGROUND: The clinical signs of neonatal sepsis are nonspecific and therefore antibiotic treatment is often initiated in clinically suspected cases. This approach causes concern in regard to possible overuse of antibiotics in newborns. Metabolomics is an emerging field of focus for neonatologists due to its potential phenotypical insight into cellular and metabolic processes, contributing to or resulting in disease in addition to having the potential to improve diagnosis. <p>OBJECTIVES: The purpose of this systematic review is to summarize current knowledge on metabolomics in neonatal infections, with a particular focus on how this method can contribute to identify sepsis in preterm and term infants. The main objective of the review will be on urine and blood metabolomics and the use or possible use of urine/blood metabolomics in clinical practice. <p>METHODS: A systematic literature search was performed in the databases MEDLINE and EMBASE up to the 1st of August 2020. We included studies that assessed neonatal sepsis on the following outcomes; (1) change in the metabolism compered to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers. The study is registered in an international prospective register of systematic reviews; PROSPERO ID: CRD42020164454. <p>RESULTS: The search identified in total 703 articles. 524 articles were screened after duplicates and triplicates were removed. 15 articles were assessed for eligibility. We included 3 studies, including a total of 71 newborns, that met the inclusion criteria. One study was included from the reference list of a literature review. The study did not conduct statistical analysis on the small neonatal group (n = 7), but had a large group of infants from 1 month up to one year (n = 46). This group of infants was considered to have a metabolomic profile likely to be comparable to the neonates, so it was included in the qualitative analysis of the systematic review. The studies used different diagnostic criteria and had small study samples. Three studies conducted untargeted metabolomics, while one study conducted both untargeted and targeted metabolomics. There was a significant difference in the metabolomic profile in septic neonates and infants compared to controls. All included studies found alteration in the glucose and lactate metabolism. <p>CONCLUSION: The identified biomarkers in the included studies have yet to be validated in large-scale multicentre studies. In regard to neonatal sepsis, more large-scale standardised studies are needed in both untargeted and targeted metabolomics. In addition, future studies should consider alternative methods like the hybrid approaches of NMR/MS.