Untargeted and Targeted Metabolomic Profiling of Preterm Newborns with EarlyOnset Sepsis: A Case-Control Study

Overview

Journal Metabolites

Publisher MDPI

Date 2021 Mar 6

PMID 33670629

Citations 11

Authors

Veronica Mardegan

Giuseppe Giordano

Matteo Stocchero

Paola Pirillo

Gabriele Poloniato

Enrica Donadel

Sabrina Salvadori

Carlo Giaquinto

Elena Priante

Eugenio Baraldi

Affiliations

Soon will be listed here.

Abstract

Sepsis is a major concern in neonatology, but there are no reliable biomarkers for its early diagnosis. The aim of the study was to compare the metabolic profiles of plasma and urine samples collected at birth from preterm neonates with and without earlyonset sepsis (EOS) to identify metabolic perturbations that might orient the search for new early biomarkers. All preterm newborns admitted to the neonatal intensive care unit were eligible for this proof-of-concept, prospective case-control study. Infants were enrolled as "cases" if they developed EOS, and as "controls"if they did not. Plasma samples collected at birth and urine samples collected within 24 h of birth underwent untargeted and targeted metabolomic analysis using mass spectrometry coupled with ultra-performance liquid chromatography. Univariate and multivariate statistical analyses were applied. Of 123 eligible newborns, 15 developed EOS. These 15 newborns matched controls for gestational age and weight. Metabolomic analysis revealed evident clustering of the cases versus controls, with the glutathione and tryptophan metabolic pathways markedly disrupted in the former. In conclusion, neonates with EOS had a metabolic profile at birth that clearly distinguished them from those without sepsis, and metabolites of glutathione and tryptophan pathways are promising as new biomarkers of neonatal sepsis.

Citing Articles

Development and internal validation of a metabolism-related model for predicting 30-day mortality in neonatal sepsis.

Tu X, Chen J, Liu W BMC Infect Dis. 2025; 25(1):121.

PMID: 39871138 PMC: 11771113. DOI: 10.1186/s12879-025-10527-z.

Does preeclampsia impact the gut microbiota of preterm offspring during early infancy?.

Chen Y, Yi Z, Yu H, Wu X, Wang J, Nie C J Transl Med. 2025; 23(1):84.

PMID: 39828685 PMC: 11744873. DOI: 10.1186/s12967-025-06120-2.

Metabolic biomarkers of neonatal sepsis: identification using metabolomics combined with machine learning.

Bian Z, Zha X, Chen Y, Chen X, Yin Z, Xu M Front Cell Dev Biol. 2024; 12:1491065.

PMID: 39498415 PMC: 11532037. DOI: 10.3389/fcell.2024.1491065.

Neonatal Sepsis: Aetiology, Pathophysiology, Diagnostic Advances and Management Strategies.

Raturi A, Chandran S Clin Med Insights Pediatr. 2024; 18:11795565241281337.

PMID: 39371316 PMC: 11452898. DOI: 10.1177/11795565241281337.

The Impact of Antenatal Corticosteroids on the Metabolome of Preterm Newborns: An Untargeted Approach.

Valerio E, Meneghelli M, Stocchero M, Galderisi A, Visentin S, Bonadies L Int J Mol Sci. 2024; 25(11).

PMID: 38892043 PMC: 11172597. DOI: 10.3390/ijms25115860.

References

Vogel L . Sepsis kills one million newborns a year: WHO. CMAJ. 2017; 189(40):E1272. PMC: 5636636. DOI: 10.1503/cmaj.109-5504. View

Santamaria F, Montella S, Stocchero M, Pirillo P, Bozzetto S, Giordano G . Effects of pidotimod and bifidobacteria mixture on clinical symptoms and urinary metabolomic profile of children with recurrent respiratory infections: a randomized placebo-controlled trial. Pulm Pharmacol Ther. 2019; 58:101818. DOI: 10.1016/j.pupt.2019.101818. View

Dong H, Cao H, Zheng H . Pathogenic bacteria distributions and drug resistance analysis in 96 cases of neonatal sepsis. BMC Pediatr. 2017; 17(1):44. PMC: 5286853. DOI: 10.1186/s12887-017-0789-9. View

Hendrikx T, Schnabl B . Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J Intern Med. 2019; 286(1):32-40. DOI: 10.1111/joim.12892. View

Collado M, Cernada M, Neu J, Perez-Martinez G, Gormaz M, Vento M . Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants. Pediatr Res. 2015; 77(6):726-31. DOI: 10.1038/pr.2015.54. View

Das A, Shukla S, Rahman N, Gunzler D, Abughali N . Clinical Indicators of Late-Onset Sepsis Workup in Very Low-Birth-Weight Infants in the Neonatal Intensive Care Unit. Am J Perinatol. 2016; 33(9):856-60. DOI: 10.1055/s-0036-1579648. View

Liu Z, Yin P, Amathieu R, Savarin P, Xu G . Application of LC-MS-based metabolomics method in differentiating septic survivors from non-survivors. Anal Bioanal Chem. 2016; 408(27):7641-7649. DOI: 10.1007/s00216-016-9845-9. View

Stewart C, Embleton N, Marrs E, Smith D, Fofanova T, Nelson A . Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017; 5(1):75. PMC: 5508794. DOI: 10.1186/s40168-017-0295-1. View

Khan A, Morris S, Bhutta Z . Neonatal and Perinatal Infections. Pediatr Clin North Am. 2017; 64(4):785-798. DOI: 10.1016/j.pcl.2017.03.008. View

10.

Chauhan N, Tiwari S, Jain U . Potential biomarkers for effective screening of neonatal sepsis infections: An overview. Microb Pathog. 2017; 107:234-242. DOI: 10.1016/j.micpath.2017.03.042. View

11.

Lyons J, Rauh-Pfeiffer A, Lu X, Zurakowski D, Curley M, Collier S . Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients. Crit Care Med. 2001; 29(4):870-7. DOI: 10.1097/00003246-200104000-00036. View

12.

Seymour C, Yende S, Scott M, Pribis J, Mohney R, Bell L . Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study. Intensive Care Med. 2013; 39(8):1423-34. PMC: 3932707. DOI: 10.1007/s00134-013-2935-7. View

13.

Madan J, Salari R, Saxena D, Davidson L, OToole G, Moore J . Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012; 97(6):F456-62. PMC: 3724360. DOI: 10.1136/fetalneonatal-2011-301373. View

14.

Ambroggio L, Florin T, Shah S, Ruddy R, Yeomans L, Trexel J . Emerging Biomarkers of Illness Severity: Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin-Resistant Staphylococcus aureus Pneumonia. Pharmacotherapy. 2017; 37(9):1033-1042. PMC: 5600674. DOI: 10.1002/phar.1973. View

15.

Evangelatos N, Bauer P, Reumann M, Satyamoorthy K, Lehrach H, Brand A . Metabolomics in Sepsis and Its Impact on Public Health. Public Health Genomics. 2018; 20(5):274-285. DOI: 10.1159/000486362. View

16.

Viant M, Kurland I, Jones M, Dunn W . How close are we to complete annotation of metabolomes?. Curr Opin Chem Biol. 2017; 36:64-69. PMC: 5337156. DOI: 10.1016/j.cbpa.2017.01.001. View

17.

Dong Y, Speer C . Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2014; 100(3):F257-63. PMC: 4413803. DOI: 10.1136/archdischild-2014-306213. View

18.

Fleischmann-Struzek C, Goldfarb D, Schlattmann P, Schlapbach L, Reinhart K, Kissoon N . The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018; 6(3):223-230. DOI: 10.1016/S2213-2600(18)30063-8. View

19.

Langley R, Tsalik E, van Velkinburgh J, Glickman S, Rice B, Wang C . An integrated clinico-metabolomic model improves prediction of death in sepsis. Sci Transl Med. 2013; 5(195):195ra95. PMC: 3924586. DOI: 10.1126/scitranslmed.3005893. View

20.

Su L, Huang Y, Zhu Y, Xia L, Wang R, Xiao K . Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach. BMJ Open Respir Res. 2015; 1(1):e000056. PMC: 4265126. DOI: 10.1136/bmjresp-2014-000056. View