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nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis—protocol for a prospective multicohort study

Mallinath Chakraborty Orcid Logo, Patrícia R S Rodrigues, W John Watkins, Angela Hayward, Alok Sharma, Rachel Hayward, Elisa Smit, Rebekka Jones, Nitin Goel, Amar Asokkumar, Jennifer Calvert, David Odd, Ian Morris, Cora Doherty, Sian Elliott, Angela Strang, Robert Andrews, Summia Zaher, Simran Sharma Orcid Logo, Sarah Bell, Siva Oruganti, Claire Smith, Judith Orme, Sarah Edkins, Marie Craigon, Daniel White, Widad Dantoft Orcid Logo, Luke Davies Orcid Logo, Linda Moet, James E McLaren, Samantha Clarkstone, Gareth L Watson, Kerenza Hood, Sailesh Kotecha Orcid Logo, B. Paul Morgan, Valerie B O’Donnell, Peter Ghazal Orcid Logo

BMJ Open, Volume: 11, Issue: 12, Start page: e050100

Swansea University Author: Luke Davies Orcid Logo

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Abstract

Introduction Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity.A combination of machine learning, statistical and deep pathway biology analyses led to the identification of...

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Published in: BMJ Open
ISSN: 2044-6055 2044-6055
Published: BMJ 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61694
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Abstract: Introduction Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity.A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work.Methods and analysis This multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)—1084 with suspected early—or late-onset sepsis, and 361 controls—over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis.Ethics and dissemination The study has received research ethics committee approval from the Wales Research Ethics Committee 2 (reference 19/WA/0008) and operational approval from Health and Care Research Wales. Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites.Trial registration number NCT03777670
College: Faculty of Medicine, Health and Life Sciences
Funders: The study is funded by a Ser Cymru grant from Welsh Government and EU/ERDF funds to Professor Peter Ghazal. MC was partly supported by a grant from Health and Care Research Wales (CRTA 16–04).
Issue: 12
Start Page: e050100