Elevated fecal calprotectin as a biomarker of sepsis in preterm neonates: A cross-sectional study
Keywords:
newborn, neonatal sepsis, feces, calprotectin, prematureAbstract
Background and aim: Fecal Calprotectin (FC) is used to determine the presence of infection in the intestine. Some studies have found high concentrations in sepsis infants with necrotizing enterocolitis but have not compared those with sepsis and without sepsis. This study evaluated the difference between FC levels in sepsis and without sepsis. Methods: A cross-sectional study was conducted. Infants aged 0 to 14 days with gestational age 28-36 weeks consist of the patient who was diagnosed with sepsis and without sepsis based on the European Medicines Agency (EMA) score. Clinical and biochemical data were collected from medical records. Fecal samples were analyzed for FC levels using the ELISA method. Results: We enrolled 88 neonates consisting of 40 neonates with sepsis and 48 neonates without sepsis. FC was higher in the sepsis infants’ group than in healthy infants (P<0.05). Multivariate analysis showed no variables significantly determining the FC level in sepsis infants. Conclusions: Preterm neonates with sepsis have higher FC levels than preterm neonates without sepsis.References
1. Perez K, Puia-Dumitrescu M, Comstock BA, et al. Patterns of infections among extremely preterm infants. J Clin Med. 2023;12(7):2703. doi: 10.3390/jcm12072703
2. Ji H, Yu Y, Huang L, et al. Pathogen distribution and antimicrobial resistance of early onset sepsis in very premature infants: a real-world study. Infect Dis Ther. 2022;11(5):1935–47. doi: 10.1007/s40121-022-00688-8
3. Goh GL, Lim CSE, Sultana R, De La Puerta R, Rajadurai VS, Yeo KT. Risk factors for mortality from late-onset sepsis among preterm very-low-birthweight infants: a single-center cohort study from Singapore. Front Pediatr. 2022;9:801955. doi: 10.3389/fped.2021.801955
4. Santos RP, Tristram D. A practical guide to the diagnosis, treatment, and prevention of neonatal infections. Pediatr Clin North Am. 2015;62(2):491–508. doi: 10.1016/j.pcl.2014.11.010
5. Dobryk DS, Dobryanskyy DO. Fecal calprotectin, lactoferrin and morbidity associated with immature digestive tract in preterm infants. Mod Pediatr Ukr. 2022;7(127):38–45. doi: 10.15574/sp.2022.127.38
6. Decembrino L, De Amici M, Pozzi M, De Silvestri A, Stronati M. Serum calprotectin: a potential biomarker for neonatal sepsis. J Immunol Res. 2015;2015:1–4. doi: 10.1155/2015/147973
7. Simm M, Söderberg E, Larsson A, et al. Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study. Biomark Med. 2016;10(8):811–8. doi: 10.2217/bmm-2016-0032
8. Larsson A, Tydén J, Johansson J, et al. Calprotectin is superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. Scand J Clin Lab Invest. 2020;80(2):156–61. doi: 10.1080/00365513.2019.1703216
9. Thibault MP, Tremblay É, Horth C, et al. Lipocalin-2 and calprotectin as stool biomarkers for predicting necrotizing enterocolitis in premature neonates. Pediatr Res. 2022;91(1):129–36. doi: 10.1038/s41390-021-01680-7
10. Pupysheva AF, Savelyeva EI, Piskunova VV, et al. Fecal calprotectin levels dynamics in newborns with high-risk of necrotizing enterocolitis. Pediatr Pharmacol (New York). 2023;20(1):51–5. doi: 10.15690/pf.v20i1.2529
11. Gogtay N. Principles of sample size calculation. Indian J Ophthalmol. 2010;58(6):517. doi: 10.4103/0301-4738.71692
12. Calculator.net. Sample size calculator. 2023. https://www.calculator.net/sample-size-calculator.html
13. Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard score, expanded to include extremely premature infants. J Pediatr. 1991;119(3):417–23. doi: 10.1016/S0022-3476(05)82056-6
14. Quinn JA, Munoz FM, Gonik B, et al. Preterm birth: case definition & guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine. 2016;34(49):6047–56. doi: 10.1016/j.vaccine.2016.03.045
15. Cutland CL, Lackritz EM, Mallett-Moore T, et al. Low birth weight: case definition & guidelines for data collection, analysis, and presentation of maternal immunization safety data. Vaccine. 2017;35(48):6492–500. doi: 10.1016/j.vaccine.2017.01.049
16. Tuzun F, Ozkan H, Cetinkaya M, et al. Is European Medicines Agency (EMA) sepsis criteria accurate for neonatal sepsis diagnosis or do we need new criteria? Bhatt GC, ed. PLoS One. 2019;14(6):e0218002. doi: 10.1371/journal.pone.0218002
17. Yilmaz A, Kaya N, Gonen I, Uygur A, Perk Y, Vural M. Evaluating of neonatal early onset sepsis through lactate and base excess monitoring. Sci Rep. 2023;13(1):14837. doi: 10.1038/s41598-023-41776-0
18. Goold E, Pearson L, Johnson LM. Can fecal calprotectin serve as a screen for necrotizing enterocolitis in infants? Clin Biochem. 2020;84:51–4. doi: 10.1016/j.clinbiochem.2020.06.015
19. Arfan M, Mariana N, Hamid F, et al. Calculating rectal nerve sheath diameter of anorectal malformations using S100 protein. Chirurgia (Bucur). 2024;37(5). doi: 10.23736/s0394-9508.23.05664-4
20. Wu M, Deng Y, Wang X, He B, Wei F, Zhang Y. Development of risk prediction nomogram for neonatal sepsis in Group B Streptococcus-colonized mothers: a retrospective study. Sci Rep. 2024;14(1):5629. doi: 10.1038/s41598-024-55783-2
21. Utomo M, Harum N, Nurrosyida K, Arif Sampurna M, Yuliaputri Aden T. The association between birth route and early/late onset neonatal sepsis in term infants: a case-control study in the NICU of a tertiary hospital in East Java, Indonesia. Iran J Neonatol. 2022;13(4). doi: 10.22038/ijn.2022.63955.2237
22. Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence. 2014;5(1):12–9. doi: 10.4161/viru.26982
23. Azis Z, Cangara MH, Zainuddin AA, Wahid S, Mariana N, Miskad UA. Immunohistochemical diagnostic value of calretinin in Hirschprung disease. Nusant Med Sci J. 2023:27–35. doi: 10.20956/nmsj.vi.20000
24. Castanheira C, Corley KTT. The influence of sex in the incidence and outcome of neonatal sepsis in horses: a retrospective study, 2008–2016. Equine Vet J. 2018;50. doi: 10.1111/evj.38_13008
25. Belachew A, Tewabe T. Neonatal sepsis and its association with birth weight and gestational age among admitted neonates in Ethiopia: systematic review and meta-analysis. BMC Pediatr. 2020;20(1):55. doi: 10.1186/s12887-020-1949-x
26. Hamid NF, Ebrahim MEE, Alsharari NMT, Alyasi ASM, Rizk MMM. Neonatal sepsis in association with birth weight, gestational age, and mode of delivery in Saudi Arabia: a systematic review and meta-analysis. Med Sci. 2021;25(111):1071–9.
27. Matsas A, Panopoulou P, Antoniou N, et al. Chronic stress in pregnancy is associated with low birth weight: a meta-analysis. J Clin Med. 2023;12(24):7686. doi: 10.3390/jcm12247686
28. Rowe-Murray HJ, Fisher JRW. Baby friendly hospital practices: cesarean section is a persistent barrier to early initiation of breastfeeding. Birth. 2002;29(2):124–31. doi: 10.1046/j.1523-536x.2002.00172.x
29. Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello MG. The infant microbiome development: mom matters. Trends Mol Med. 2015;21(2):109–17. doi: 10.1016/j.molmed.2014.12.002
30. Rosti L, Braga M, Fulcieri C, Sammarco G, Manenti B, Costa E. Formula milk feeding does not increase the release of the inflammatory marker calprotectin, compared to human milk. Pediatr Med Chir. 2011;33(4):178–81
31. Gao R, Tomlinson M, Walker C. Correlation of Pirani and Dimeglio scores with number of Ponseti casts required for clubfoot correction. J Pediatr Orthop. 2014;34(6):639–42. doi: 10.1097/bpo.0000000000000182
32. Hoskin TS, Crowther JM, Cheung J, et al. Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis. Redox Biol. 2019;24:101202. doi: 10.1016/j.redox.2019.101202
33. Kido J, Kido R, Suryono, Kataoka M, Fagerhol MK, Nagata T. Calprotectin release from human neutrophils is induced by Porphyromonas gingivalis lipopolysaccharide via the CD14–Toll-like receptor–nuclear factor κB pathway. J Periodontal Res. 2003;38(6):557–63. doi: 10.1034/j.1600-0765.2003.00691.x
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Lory Iswanto Latif, Andi Dwi Bahagia Febriani, Ema Alasiry, Aidah Juliaty A Baso, Hadia Angriani Machmoed, Jusli

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

