Home Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth
Article
Licensed
Unlicensed Requires Authentication

Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth

  • Ebe D’Adamo , Gabriella Levantini , Michela Librandi , Valentina Botondi , Laura Di Ricco , Sara De Sanctis , Cynzia Spagnuolo , Francesca Gazzolo , Danilo AW Gavilanes , Patrizia Di Gregorio , Jessica Di Monte , Maria Chiara Strozzi , Antonio Maconi , Maurizio Cassinari , Roberta Libener and Diego Gazzolo EMAIL logo
Published/Copyright: February 2, 2024
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 8

Abstract

Objectives

Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP).

Methods

We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded.

Results

No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed.

Conclusions

The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

Keywords: presepsin; hypoxia; newborns; intrauterine growth retardation
Corresponding Author: Prof. Diego Gazzolo, Neonatal Intensive Care Unit, G. d’Annunzio University, 65100 Chieti, Italy, Phone: +39 0871 358219, E-mail:

  1. Research ethics: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of ASO SS Antonio, Biagio and C. Arrigo, Alessandria, Italy (Presap.ASO.Neonat.19.02/23.05.19).

  2. Informed consent: Informed consent was obtained from all the individuals included in this study, or from their legal guardians or wards.

  3. Author contributions: EDA, GL, ML, VB, LDR, SDS, CS, FG, DAWG, PDG, JDM, MCS, AM, MS and RB contributed to the conceptualization, investigation and writing of the original draft. DG contributed to the project administration, conceptualization, investigation, supervision and writing, review, and editing. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. All the authors have read and agreed to the published version of the manuscript.

  4. Competing interests: The funding organizations played no role in the study design; in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the report for publication.

  5. Research funding: This work is part of the I.O. PhD International Program under the auspices of the Italian Society of Neonatology and was partially supported by grants to DG from “I Colori della Vita Foundation” 2/2018, and Danone unconditioned support 3/2019. We thank PHC Europe BV, The Netherlands, for scientific support, and Gepa S.r.l, Italy, for providing analysis kits. The funding organizations played no role in the study design; in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the report for publication.

  6. Data availability: Not applicable.

References

1. Deshmukh, M, Mehta, S, Patole, S. Sepsis calculator for neonatal early onset sepsis – a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2021;34:1832–40. https://doi.org/10.1080/14767058.2019.1649650.Search in Google Scholar PubMed

2. Botondi, V, D’Adamo, E, Plebani, M, Trubiani, O, Perrotta, M, Di Ricco, L, et al.. Perinatal presepsin assessment: a new sepsis diagnostic tool? Clin Chem Lab Med 2022;60:1136–44. https://doi.org/10.1515/cclm-2022-0277.Search in Google Scholar PubMed

3. van Maldeghem, I, Nusman, CM, Visser, DH. Soluble CD14 subtype (sCD14-ST) as biomarker in neonatal early-onset sepsis and late-onset sepsis: a systematic review and meta-analysis. BMC Immunol 2019;20:17. https://doi.org/10.1186/s12865-019-0298-8.Search in Google Scholar PubMed PubMed Central

4. Pugni, L, Pietrasanta, C, Milani, S, Vener, C, Ronchi, A, Falbo, M, et al.. Presepsin (Soluble CD14 Subtype): reference ranges of a new sepsis marker in term and preterm neonates. PLoS One 2015;10:e0146020. https://doi.org/10.1371/journal.pone.0146020.Search in Google Scholar PubMed PubMed Central

5. Mussap, M, Puxeddu, E, Burrai, P, Noto, A, Cibecchini, F, Testa, M, et al.. Soluble CD14 subtype (sCD14-ST) presepsin in critically ill preterm newborns: preliminary reference ranges. J Matern Neonatal Med 2012;25:51–3. https://doi.org/10.3109/14767058.2012.717462.Search in Google Scholar PubMed

6. Koh, JH, Lee, S, Kim, HS, Lee, K, Lee, CS, Yoo, SA, et al.. Development of monitoring system for assessing rheumatoid arthritis within 5 minutes using a drop of biofluids. J Clin Med 2020;9:3499. https://doi.org/10.3390/jcm9113499.Search in Google Scholar PubMed PubMed Central

7. Nishana, E, Bhat, SS, Sahana, KS, Hegde, SK, Bhat, V, Kalal, BS. Estimation of salivary sCD14 in children with early childhood caries in association with pneumonia. Rep Biochem Mol Biol 2019;8:132–8.Search in Google Scholar

8. Botondi, V, Pirra, A, Strozzi, M, Perrotta, M, Gavilanes, DAW, Di Ricco, L, et al.. Perinatal asphyxia partly affects presepsin urine levels in non-infected term infants. Clin Chem Lab Med 2022;60:793–9. https://doi.org/10.1515/cclm-2022-0027.Search in Google Scholar PubMed

9. Montaldo, P, Rosso, R, Santantonio, A, Chello, G, Giliberti, P. Presepsin for the detection of early-onset sepsis in preterm newborns. Pediatr Res 2017;81:329–34. https://doi.org/10.1038/pr.2016.217.Search in Google Scholar PubMed

10. Memar, MY, Baghi, HB. Presepsin: a promising biomarker for the detection of bacterial infections. Biomed Pharmacother 2019;111:649–56. https://doi.org/10.1016/j.biopha.2018.12.124.Search in Google Scholar PubMed

11. Maddaloni, C, De Rose, DU, Perulli, M, Martini, L, Bersani, I, Campi, F, et al.. Perinatal asphyxia does not influence presepsin levels in neonates: a prospective study. Acta Paediatr 2023. https://doi.org/10.1111/apa.17031.Search in Google Scholar PubMed

12. Kraus, CK, Nguyen, HB, Jacobsen, RC, Ledeboer, NA, May, LS, O’Neal, HRJr, et al.. Rapid identification of sepsis in the emergency department. J Am Coll Emerg Physicians Open 2023;4:e12984. https://doi.org/10.1002/emp2.12984.Search in Google Scholar PubMed PubMed Central

13. Bertino, E, Di Nicola, P, Varalda, AG, Occhi, L, Giuliani, F, Coscia, A. Neonatal growth charts. J Matern Neonatal Med 2012;25:67–9. https://doi.org/10.3109/14767058.2012.664889.Search in Google Scholar PubMed

14. Stewart, DL, Barfield, WD, Cummings, JJ, Adams-Chapman, IA, Aucott, SW, Goldsmith, JP, et al.. Updates on an at-risk population: late-preterm and early-term infants. Pediatrics 2019;144:e1–10. https://doi.org/10.1542/peds.2019-2760.Search in Google Scholar PubMed

15. ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction Ultrasound Obstet Gynecol 2020;56:298–312.10.1002/uog.22134Search in Google Scholar PubMed

16. Papile, LA, Burstein, J, Burstein, R, Koffler, H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978;92:529–34. https://doi.org/10.1016/s0022-3476(78)80282-0.Search in Google Scholar PubMed

17. D’Adamo, E, Botondi, V, Falconio, L, Giardinelli, G, Di Gregorio, P, Caputi, S, et al.. Effect of temperature on presepsin pre-analytical stability in biological fluids of preterm and term newborns. Clin Chem Lab Med 2024;62:1011–16. https://doi.org/10.1515/cclm-2023-1282.Search in Google Scholar PubMed

18. Pedroso, MA, Palmer, KR, Hodges, RJ, Costa, FDS, Rolnik, DL. Uterine artery Doppler in screening for preeclampsia and fetal growth restriction. Rev Bras Ginecol Obstet 2018;40:287–93. https://doi.org/10.1055/s-0038-1660777.Search in Google Scholar PubMed PubMed Central

19. Shah, BA, Padbury, JF. Neonatal sepsis: an old problem with new insights. Virulence 2014;5:170–8. https://doi.org/10.4161/viru.26906.Search in Google Scholar PubMed PubMed Central

20. Maddaloni, C, De Rose, DU, Santisi, A, Martini, L, Caoci, S, Bersani, I, et al.. The emerging role of presepsin (p-sep) in the diagnosis of sepsis in the critically ill infant: a literature review. Int J Mol Sci 2021;22:12154. https://doi.org/10.3390/ijms222212154.Search in Google Scholar PubMed PubMed Central

21. Zea-Vera, A, Ochoa, TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 2015;61:1–13. https://doi.org/10.1093/tropej/fmu079.Search in Google Scholar PubMed PubMed Central

22. Keij, FM, Kornelisse, RF, Tramper-Stranders, GA, Allegaert, K. Improved pathogen detection in neonatal sepsis to boost antibiotic stewardship. Future Microbiol 2020;15:461–4. https://doi.org/10.2217/fmb-2019-0334.Search in Google Scholar PubMed

23. Morad, EA, Rabie, RA, Almalky, MA, Gebriel, MG. Evaluation of procalcitonin, c-reactive protein, and interleukin-6 as early markers for diagnosis of neonatal sepsis. Int J Microbiol 2020;2020:8889086. https://doi.org/10.1155/2020/8889086.Search in Google Scholar PubMed PubMed Central

24. Sproston, NR, Ashworth, JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754–61. https://doi.org/10.3389/fimmu.2018.00754.Search in Google Scholar PubMed PubMed Central

25. Munteanu, AI, Manea, AM, Jinca, CM, Boia, M. Basic biochemical and hematological parameters in perinatal asphyxia and their correlation with hypoxic ischemic encephalopathy. Exp Ther Med 2021;21:259–66. https://doi.org/10.3892/etm.2021.9690.Search in Google Scholar PubMed PubMed Central

26. Xanthou, M, Fotopoulos, S, Mouchtouri, A, Lipsou, N, Zika, I, Sarafidou, J. Inflammatory mediators in neonatal asphyxia and infection. Acta Paediatr 2002;91:92–7. https://doi.org/10.1111/j.1651-2227.2002.tb02911.x.Search in Google Scholar PubMed

27. Yadav, P, Agarwal, K, Rani, A, Dewan, R, Chellani, H. Procalcitonin levels in maternal serum and cord blood as marker for diagnosis of early onset neonatal sepsis. Eur J Obstet Gynecol Reprod Biol X 2023;19:100221. https://doi.org/10.1016/j.eurox.2023.100221.Search in Google Scholar PubMed PubMed Central

28. Joolay, Y, Raban, S, van Wyk, J, Omar, F. The role of c-reactive protein and implications to the neonatal intensive care unit. Cham: Springer; 2023:133–53 pp.10.1007/978-3-031-07395-3_9Search in Google Scholar

29. Samsudin, I, Vasikaran, SD. Clinical utility and measurement of procalcitonin. Clin Biochem Rev 2017;38:59–68.Search in Google Scholar

30. Pham, K, Parikh, K, Heinrich, EC. Hypoxia and inflammation: insights from high-altitude physiology. Front Physiol 2021;12:676782. https://doi.org/10.3389/fphys.2021.676782.Search in Google Scholar PubMed PubMed Central

31. Tröger, B, Müller, T, Faust, K, Bendiks, M, Bohlmann, MK, Thonnissen, S, et al.. Intrauterine growth restriction and the innate immune system in preterm infants of ≤32 weeks gestation. Neonatology 2013;103:199–04. https://doi.org/10.1159/000343260.Search in Google Scholar PubMed

32. Alahakoon, TI, Medbury, H, Williams, H, Fewings, N, Wang, XM, Lee, VW. Characterization of fetal monocytes in preeclampsia and fetal growth restriction. J Perinat Med 2019;47:434–8. https://doi.org/10.1515/jpm-2018-0286.Search in Google Scholar PubMed

33. Lager, S, Sovio, U, Eddershaw, E, van der Linden, MW, Yazar, C, Cook, E, et al.. Abnormal placental CD8+ T-cell infiltration is a feature of fetal growth restriction and pre-eclampsia. J Physiol 2020;598:5555–71. https://doi.org/10.1113/jp279532.Search in Google Scholar

34. Farley, D, Tejero, ME, Comuzzie, AG, Higgins, PB, Cox, L, Werner, SL, et al.. Feto-placental adaptations to maternal obesity in the baboon. Placenta 2009;30:752–60. https://doi.org/10.1016/j.placenta.2009.06.007.Search in Google Scholar PubMed PubMed Central

35. Amarilyo, G, Oren, A, Mimouni, FB, Ochshorn, Y, Deutsch, V, Mandel, D. Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol 2011;31:30–2. https://doi.org/10.1038/jp.2010.53.Search in Google Scholar PubMed

36. Hromadnikova, I, Kotlabova, K, Dvorakova, L, Krofta, L. Maternal cardiovascular risk assessment 3-to-11 years postpartum in relation to previous occurrence of pregnancy-related complications. J Clin Med 2019;8:544. https://doi.org/10.3390/jcm8040544.Search in Google Scholar PubMed PubMed Central

37. Kara, AE, Guney, G, Tokmak, A, Ozaksit, G. The role of inflammatory markers hs-CRP, sialic acid, and IL-6 in the pathogenesis of preeclampsia and intrauterine growth restriction. Eur Cytokine Netw 2019;30:29–33. https://doi.org/10.1684/ecn.2019.0423.Search in Google Scholar PubMed

38. Haedersdal, S, Salvig, JD, Aabye, M, Thorball, CW, Ruhwald, M, Ladelund, S, et al.. Inflammatory markers in the second trimester prior to clinical onset of preeclampsia, intrauterine growth restriction, and spontaneous preterm birth. Inflammation 2013;36:907–13. https://doi.org/10.1007/s10753-013-9619-x.Search in Google Scholar PubMed

39. Erkenekli, K, Keskin, U, Uysal, B, Kurt, YG, Sadir, S, Çayci, T, et al.. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction. J Obstet Gynaecol 2015;35:225–8. https://doi.org/10.3109/01443615.2014.948818.Search in Google Scholar PubMed

40. De Rose, DU, Perri, A, Auriti, C, Gallini, F, Maggio, L, Fiori, B, et al.. Time to positivity of blood cultures could inform decisions on antibiotics administration in neonatal early-onset sepsis. Antibiotics 2021;10:123. https://doi.org/10.3390/antibiotics10020123.Search in Google Scholar PubMed PubMed Central

Received: 2023-11-16
Accepted: 2024-01-24
Published Online: 2024-02-02
Published in Print: 2024-07-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Analytical performance specifications – moving from models to practical recommendations
  4. Opinion Papers
  5. What the Milan conference has taught us about analytical performance specification model definition and measurand allocation
  6. The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine
  7. How clinical laboratories select and use Analytical Performance Specifications (APS) in Italy
  8. Outcome-based analytical performance specifications: current status and future challenges
  9. Analytical performance specifications based on biological variation data – considerations, strengths and limitations
  10. State-of-the-art model for derivation of analytical performance specifications: how to define the highest level of analytical performance technically achievable
  11. Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability
  12. When bias becomes part of imprecision: how to use analytical performance specifications to determine acceptability of lot-lot variation and other sources of possibly unacceptable bias
  13. Using analytical performance specifications in a medical laboratory
  14. Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems
  15. Applying the Milan models to setting analytical performance specifications – considering all the information
  16. Guidelines and Recommendations
  17. Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary
  18. General Clinical Chemistry and Laboratory Medicine
  19. Assessment of accuracy of laboratory testing results, relative to peer group consensus values in external quality control, by bivariate z-score analysis: the example of D-Dimer
  20. The stability of 65 biochemistry analytes in plasma, serum, and whole blood
  21. Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population
  22. In vitro, in vivo metabolism and quantification of the novel synthetic opioid N-piperidinyl etonitazene (etonitazepipne)
  23. Quantification of blood glial fibrillary acidic protein using a second-generation microfluidic assay. Validation and comparative analysis with two established assays
  24. Association of prehospital lactate levels with base excess in various emergencies – a retrospective study
  25. Reference Values and Biological Variations
  26. Stability of ten serum tumor markers after one year of storage at −18°C
  27. Variations in tumor growth, intra-individual biological variability, and the interpretation of changes
  28. Cancer Diagnostics
  29. N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma
  30. Cardiovascular Diseases
  31. Reference intervals for high sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide in children and adolescents on the Siemens Atellica
  32. Infectious Diseases
  33. Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth
  34. Letters to the Editor
  35. AWMF statement on medical services in laboratory diagnostics and pathology with regard to the IVDR
  36. An outline of measurement uncertainty of total protein in urine estimated according to the ISO Technical Specification 20914
  37. Early diagnosis of severe illness in an outpatient – the Sysmex XN’s neutrophil reactivity parameter
  38. Analytical and diagnostic performance of Theradiag i-Tracker assays on IDS-iSYS for infliximab and adalimumab therapeutic drug monitoring
  39. Improving the diagnosis of AATD with aid of serum protein electrophoresis: a prospective, multicentre, validation study
  40. Cerebrospinal fluid kappa free light chains in patients with tumefactive demyelination
  41. Diagnostic value of quantitative chemiluminescence immunoassay for anti-gp210 and anti-sp100 antibodies in primary biliary cholangitis
https://doi.org/10.1515/cclm-2023-1308
Keywords for this article
presepsin; hypoxia; newborns; intrauterine growth retardation

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Analytical performance specifications – moving from models to practical recommendations
  4. Opinion Papers
  5. What the Milan conference has taught us about analytical performance specification model definition and measurand allocation
  6. The role of analytical performance specifications in international guidelines and standards dealing with metrological traceability in laboratory medicine
  7. How clinical laboratories select and use Analytical Performance Specifications (APS) in Italy
  8. Outcome-based analytical performance specifications: current status and future challenges
  9. Analytical performance specifications based on biological variation data – considerations, strengths and limitations
  10. State-of-the-art model for derivation of analytical performance specifications: how to define the highest level of analytical performance technically achievable
  11. Analytical performance specifications for combined uncertainty budget in the implementation of metrological traceability
  12. When bias becomes part of imprecision: how to use analytical performance specifications to determine acceptability of lot-lot variation and other sources of possibly unacceptable bias
  13. Using analytical performance specifications in a medical laboratory
  14. Issues in assessing analytical performance specifications in healthcare systems assembling multiple laboratories and measuring systems
  15. Applying the Milan models to setting analytical performance specifications – considering all the information
  16. Guidelines and Recommendations
  17. Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary
  18. General Clinical Chemistry and Laboratory Medicine
  19. Assessment of accuracy of laboratory testing results, relative to peer group consensus values in external quality control, by bivariate z-score analysis: the example of D-Dimer
  20. The stability of 65 biochemistry analytes in plasma, serum, and whole blood
  21. Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population
  22. In vitro, in vivo metabolism and quantification of the novel synthetic opioid N-piperidinyl etonitazene (etonitazepipne)
  23. Quantification of blood glial fibrillary acidic protein using a second-generation microfluidic assay. Validation and comparative analysis with two established assays
  24. Association of prehospital lactate levels with base excess in various emergencies – a retrospective study
  25. Reference Values and Biological Variations
  26. Stability of ten serum tumor markers after one year of storage at −18°C
  27. Variations in tumor growth, intra-individual biological variability, and the interpretation of changes
  28. Cancer Diagnostics
  29. N-linked glycosylation of the M-protein variable region: glycoproteogenomics reveals a new layer of personalized complexity in multiple myeloma
  30. Cardiovascular Diseases
  31. Reference intervals for high sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide in children and adolescents on the Siemens Atellica
  32. Infectious Diseases
  33. Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth
  34. Letters to the Editor
  35. AWMF statement on medical services in laboratory diagnostics and pathology with regard to the IVDR
  36. An outline of measurement uncertainty of total protein in urine estimated according to the ISO Technical Specification 20914
  37. Early diagnosis of severe illness in an outpatient – the Sysmex XN’s neutrophil reactivity parameter
  38. Analytical and diagnostic performance of Theradiag i-Tracker assays on IDS-iSYS for infliximab and adalimumab therapeutic drug monitoring
  39. Improving the diagnosis of AATD with aid of serum protein electrophoresis: a prospective, multicentre, validation study
  40. Cerebrospinal fluid kappa free light chains in patients with tumefactive demyelination
  41. Diagnostic value of quantitative chemiluminescence immunoassay for anti-gp210 and anti-sp100 antibodies in primary biliary cholangitis
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 8.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-1308/html
Scroll to top button