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Peer-reviewedCC BY 4.0Frontiers in Immunology

Serum and cerebrospinal fluid biomarkers for risk stratification of hospitalized neonates and young infants with suspected serious bacterial infections: a secondary analysis of a prospective cohort study

  • Chaymae El Abbass1,2
  • Luis Alberto Benegas3,4
  • Andrea Alemany3
  • Cristina Garcia-Mauriño3
  • Ilham Elouardighi1,2
  • Imane Zizi1,2
  • Najat Amalik1,2
  • Lamya El Laziji1,2
  • Sobha El Ftouh5
  • Rachid Babi5
  • Khalid Bounagua5
  • Nouhayla Bouali6
16 more authors
  • Sara Ajanovic3,7,8,9,10
  • Sara Arias3
  • Dan Ouchi3
  • Fio Vialard3
  • David Torres-Fernandez3,7
  • Pere Millat-Martinez3
  • Diana Barrios3
  • Rosauro Varo3,8,11,12
  • Kevin C. Kain13
  • Ruth Aguilar3
  • Carlota Dobaño3,14
  • Gemma Moncunill3,14
  • Houssain Tligui1,5
  • Bàrbara Baro3,8
  • Quique Bassat3,7,8,12,15,16,17
  • Amina Barkat1,2
17 affiliations
  1. 1Research Team on Health and Nutrition of Mother and Child, Laboratory of Biostatistics, Clinical Research and Epidemiology, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat
  2. 2National Reference Center for Neonatology and Nutrition, Children’s Hospital, Ibn Sina University Hospital Centre
  3. 3ISGlobal
  4. 4Department of Preventive Medicine and Epidemiology, Hospital Clínic
  5. 5Research Laboratory of Ibn Sina University Hospital Centre - Faculty of Medicine and Pharmacy, Mohammed V University in Rabat
  6. 6Mohammed VI International School of Public Health, Mohammed VI University of Sciences and Health (UM6SS)
  7. 7Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB)
  8. 8Centro de Investigação em Saúde de Manhiça (CISM)
  9. 9Pediatric Infectious Diseases and Immunodeficiencies Unit, Children’s Hospital, Vall d’Hebron Barcelona Hospital Campus
  10. 10Infection and Immunity in Pediatric Patients, Vall d’Hebron Research Institute
  11. 11Institut de Recerca Sant Joan de Deu, Hospital Sant Joan de Deu
  12. 12CIBER de Epidemiología y Salud Pública
  13. 13Tropical Disease Unit, University of Toronto, UHN- Toronto General Hospital
  14. 14CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III
  15. 15ICREA
  16. 16Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona
  17. 17Institut Clínic de Medicina i Dermatologia, Hospital Clínic de Barcelona
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Abstract

Background: Improved risk stratification strategies for neonates and young infants are urgently needed to reduce the substantial mortality burden associated with infectious diseases, particularly in low- and middle-income settings. Evidence supporting the use of host-response biomarkers to predict disease severity in this population remains limited.

Methods: We conducted a secondary analysis of a prospective cohort study at a National Reference Neonatology Centre in Morocco and evaluated the prognostic performance of host-response biomarkers measured in serum and cerebrospinal fluid (CSF) to predict in-hospital mortality among hospitalized sick neonates and young infants (<2 months). Twenty-one biomarkers of immune activation, endothelial dysfunction, and neuronal injury were measured using Luminex and compared head-to-head.

Results: Among 179 participants with available serum and/or CSF samples included in this analysis, 9% died during hospitalization (11/136 in the serum sample set, and 12/148 in the CSF sample set). In serum, lower concentrations of TRAIL and higher concentrations of Angpt-2, IL-8, and uPAR, were associated with in-hospital death, with TRAIL showing the strongest prognostic performance (AUROC 0.86; 95% CI 0.78-0.93). In CSF, PCT was the strongest predictor of severe progression for in-hospital death (AUROC 0.87; 95% CI 0.80-0.95), whereas higher levels of IL-6, IL-12p70, TNFR1, TREM-1, Angpt-1, NGAL, and NSE were associated with higher odds of probable or laboratory-confirmed meningitis.

Discussion: Serum levels of TRAIL showed an exploratory association with disease severity in hospitalized neonates and young infants with suspected serious bacterial infections. Larger multicenter studies are needed to validate these findings using multiple biological matrices, characterize kinetics, and determine whether these markers may have clinical utility for risk stratification in this vulnerable population.

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Cite

BibTeXRIS
BibTeX
@article{abbass2026serum,
  title = {{Serum and cerebrospinal fluid biomarkers for risk stratification of hospitalized neonates and young infants with suspected serious bacterial infections: a secondary analysis of a prospective cohort study}},
  author = {Chaymae El Abbass and Luis Alberto Benegas and Andrea Alemany and Cristina Garcia-Mauriño and Ilham Elouardighi and Imane Zizi and Najat Amalik and Lamya El Laziji and Sobha El Ftouh and Rachid Babi and Khalid Bounagua and Nouhayla Bouali and Sara Ajanovic and Sara Arias and Dan Ouchi and Fio Vialard and David Torres-Fernandez and Pere Millat-Martinez and Diana Barrios and Rosauro Varo and Kevin C. Kain and Ruth Aguilar and Carlota Dobaño and Gemma Moncunill and Houssain Tligui and Bàrbara Baro and Quique Bassat and Amina Barkat},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1873954},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873954/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Serum and cerebrospinal fluid biomarkers for risk stratification of hospitalized neonates and young infants with suspected serious bacterial infections: a secondary analysis of a prospective cohort study
AU  - Chaymae El Abbass
AU  - Luis Alberto Benegas
AU  - Andrea Alemany
AU  - Cristina Garcia-Mauriño
AU  - Ilham Elouardighi
AU  - Imane Zizi
AU  - Najat Amalik
AU  - Lamya El Laziji
AU  - Sobha El Ftouh
AU  - Rachid Babi
AU  - Khalid Bounagua
AU  - Nouhayla Bouali
AU  - Sara Ajanovic
AU  - Sara Arias
AU  - Dan Ouchi
AU  - Fio Vialard
AU  - David Torres-Fernandez
AU  - Pere Millat-Martinez
AU  - Diana Barrios
AU  - Rosauro Varo
AU  - Kevin C. Kain
AU  - Ruth Aguilar
AU  - Carlota Dobaño
AU  - Gemma Moncunill
AU  - Houssain Tligui
AU  - Bàrbara Baro
AU  - Quique Bassat
AU  - Amina Barkat
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1873954
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873954/full
AB  - Background: Improved risk stratification strategies for neonates and young infants are urgently needed to reduce the substantial mortality burden associated with infectious diseases, particularly in low- and middle-income settings. Evidence supporting the use of host-response biomarkers to predict disease severity in this population remains limited.  Methods: We conducted a secondary analysis of a prospective cohort study at a National Reference Neonatology Centre in Morocco and evaluated the prognostic performance of host-response biomarkers measured in serum and cerebrospinal fluid (CSF) to predict in-hospital mortality among hospitalized sick neonates and young infants (<2 months). Twenty-one biomarkers of immune activation, endothelial dysfunction, and neuronal injury were measured using Luminex and compared head-to-head.  Results: Among 179 participants with available serum and/or CSF samples included in this analysis, 9% died during hospitalization (11/136 in the serum sample set, and 12/148 in the CSF sample set). In serum, lower concentrations of TRAIL and higher concentrations of Angpt-2, IL-8, and uPAR, were associated with in-hospital death, with TRAIL showing the strongest prognostic performance (AUROC 0.86; 95% CI 0.78-0.93). In CSF, PCT was the strongest predictor of severe progression for in-hospital death (AUROC 0.87; 95% CI 0.80-0.95), whereas higher levels of IL-6, IL-12p70, TNFR1, TREM-1, Angpt-1, NGAL, and NSE were associated with higher odds of probable or laboratory-confirmed meningitis.  Discussion: Serum levels of TRAIL showed an exploratory association with disease severity in hospitalized neonates and young infants with suspected serious bacterial infections. Larger multicenter studies are needed to validate these findings using multiple biological matrices, characterize kinetics, and determine whether these markers may have clinical utility for risk stratification in this vulnerable population.
SN  - 1664-3224
ER  -