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Licensed Unlicensed Requires Authentication Published by De Gruyter May 19, 2021

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants

  • Giorgia Gasparroni , Alessandro Graziosi , Iliana Bersani , Massimo Caulo , Bashir Moataza , Hanna Aboulgar , Hala Mufeed , Iman Iskander , Maria Kornacka , Darek Gruzfeld , Andrea Dotta , Immacolata Savarese , Natalia Chukhlantseva , Lucia Gabriella Tina , Francesco Nigro , Giovanni Livolti , Fabio Galvano , Caterina Di Battista , Ebe D’Adamo , Adele Patrizia Primavera , Giuseppe Lapergola , Mariangela Conte , Rita Salomone , Marika Perrotta , Daniele Panichi , Gabriella Levantini , Milena Catenaro , Chiara Strozzi , Antonio Maconi , Giacomo Centini , Francesco Chiarelli , Francesco D’Antonio , Danilo A.W. Gavilanes and Diego Gazzolo EMAIL logo

Abstract

Objectives

The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures.

Methods

We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40–42 weeks of corrected gestational age.

Results

Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI.

Conclusions

The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.


Corresponding author: Prof. Diego Gazzolo, Neonatal Intensive Care Unit, G. d’Annunzio University, Chieti, Italy, Phone: +39 0871 358219, E-mail:

Funding source: I Colori della Vita Foundation

Acknowledgments

We thank Diasorin, Saluggia, Italy, for supporting analysis kits.

  1. 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 (principal investigator) from “I Colori della Vita Foundation,” Italy.

  2. Author contributions: Giorgia Gasparroni, Alessandro Graziosi, Ilaria Bersani, Bashir Moataza, Hanna Aboulgar, Hala Mufeed, Andrea Dotta, Immacolata Savarese, Massimo Caulo, Iman Iskander, Maria Kornacka, Darek Gruszfeld, Giovanni Livolti, Antonio Maconi, Giacomo Centini, Chiara Strozzi, Francesco Nigro, Lucia Gabriella Tina, Natalia Chukhlantseva, Danilo AW Gavilanes, Fabio Galvano, Caterina Di Battista, Rita Salomone, Giuseppe Lapergola, Daniele Panichi, Ebe D’Adamo, Mariangela Conte, Gabriella Levantini, Francesco D’Antonio, Adele Patrizia Primavera, Milena Catenaro, Marika Perrotta, Francesco Chiarelli and Diego Gazzolo made substantial contribution to conception and design of the study, acquisition, analysis and interpretation of data; authors participate in drafting the article or revising it critically. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013). The Local Ethic Committees of the Cooperative Multitask against Brain Injury of Neonates (CoMBINe) International Network approved the study protocol.

References

1. Rubens, CE, Sadovsky, Y, Muglia, L, Gravett, MG, Lackritz, E, Gravett, C. Prevention of preterm birth: harnessing science to address the global epidemic. Sci Transl Med 2014;6:262sr5. https://doi.org/10.1126/scitranslmed.3009871.Search in Google Scholar PubMed

2. Costeloe, KL, Hennessy, EM, Haider, S, Stacey, F, Marlow, N, Draper, ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012;345:e7976. https://doi.org/10.1136/bmj.e7976.Search in Google Scholar PubMed PubMed Central

3. Glass, HC, Costarino, AT, Stayer, SA, Brett, CM, Cladis, F, Davis, PJ. Outcomes for extremely premature infants. Anesth Analg 2015;120:1337–51. https://doi.org/10.1213/ane.0000000000000705.Search in Google Scholar PubMed PubMed Central

4. Szpecht, D, Szymankiewicz, M, Nowak, I, Gadzinowski, J. Intraventricular hemorrhage in neonates born before 32 weeks of gestation—retrospective analysis of risk factors. Child’s Nerv Syst 2016;32:1399–404. https://doi.org/10.1007/s00381-016-3127-x.Search in Google Scholar PubMed PubMed Central

5. Leijser, LM, de Vries, LS. Preterm brain injury: germinal matrix–intraventricular hemorrhage and post-hemorrhagic ventricular dilatation. In: Handbook of clinical neurology 2019:162:173–99.10.1016/B978-0-444-64029-1.00008-4Search in Google Scholar PubMed

6. Serpero, LD, Bellissima, V, Colivicchi, M, Sabatini, M, Frigiola, A, Ricotti, A, et al.. Next generation biomarkers for brain injury. J Matern Fetal Neonatal Med 2013;26(2 Suppl):44–9. https://doi.org/10.3109/14767058.2013.829688.Search in Google Scholar PubMed

7. Bersani, I, Pluchinotta, F, Dotta, A, Savarese, I, Campi, F, Auriti, C, et al.. Early predictors of perinatal brain damage: the role of neurobiomarkers. Clin Chem Lab Med 2020;58:471–86. https://doi.org/10.1515/cclm-2019-0725.Search in Google Scholar PubMed

8. Alshweki, A, Pérez-Muñuzuri, A, López-Suárez, O, Baña, A, Couce, ML. Relevance of urinary S100B protein levels as a short-term prognostic biomarker in asphyxiated infants treated with hypothermia. Medicine 2017;96:e8453. https://doi.org/10.1097/md.0000000000008453.Search in Google Scholar PubMed PubMed Central

9. Gazzolo, D, Florio, P, Ciotti, S, Marinoni, E, Di Iorio, R, Bruschettini, M, et al.. S100B protein in urine of preterm newborns with ominous outcome. Pediatr Res 2005;58:1170–4. https://doi.org/10.1203/01.pdr.0000185131.22985.30.Search in Google Scholar PubMed

10. Campbell, S, Thoms, A. Ultrasound measurement of the fetal head to abdomen circumference ratio in the assessment of growth retardation. BJOG An Int J Obstet Gynaecol 1977;84:165–74. https://doi.org/10.1111/j.1471-0528.1977.tb12550.x.Search in Google Scholar PubMed

11. 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

12. Kidokoro, H, Neil, JJ, Inder, TE. New MR imaging assessment tool to define brain abnormalities in very preterm infants at term. Am J Neuroradiol 2013;34:2208–14. https://doi.org/10.3174/ajnr.a3521.Search in Google Scholar

13. Prechtl, HFR. Assessment methods for the newborn infant, a critical evaluation. In: Stratton, P, editor. Psychobiology of the human newborn. Chichester: Wiley; 1982:21–52 pp.Search in Google Scholar

14. Jurgens-van der Zee, AD, Bierman-van Eendenburg, MEC, Fidler, VJ, Olinga, AA, Visch, JH, Touwen, BCL, et al.. Preterm birth, growth retardation and acidemia in relation to neurological abnormality of the newborn. Early Hum Dev 1979;3:141–54. https://doi.org/10.1016/0378-3782(79)90003-3.Search in Google Scholar

15. Jobe, AH, Bancalari, E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723–9. https://doi.org/10.1164/ajrccm.163.7.2011060.Search in Google Scholar

16. Agarwal, K, Jalali, S. Classification of retinopathy of prematurity: from then till now. Community Eye Health 2018;31:S4–7.Search in Google Scholar

17. Baudier, J, Glasser, N, Haglid, K, Gerard, D. Purification, characterization and ion binding properties of human brain S100b protein. Biochim Biophys Acta Protein Struct Mol Enzymol 1984;790:164–73. https://doi.org/10.1016/0167-4838(84)90220-6.Search in Google Scholar

18. McCrea, HJ, Ment, LR. The diagnosis, management, and postnatal prevention of intraventricular hemorrhage in the preterm neonate. Clin Perinatol 2008;35:777–92. https://doi.org/10.1016/j.clp.2008.07.014.Search in Google Scholar PubMed PubMed Central

19. Whitelaw, A. Intraventricular haemorrhage and posthaemorrhagic hydrocephalus: pathogenesis, prevention and future interventions. Semin Neonatol 2001;6:135–46. https://doi.org/10.1053/siny.2001.0047.Search in Google Scholar PubMed

20. Volpe, JJ. Intrachranial hemorrhage: germinal matrix-intraventricular hemorrhage of premature infant. In: Neurology of the newborn, 5th ed. Philadelphia: Saunders; 2018, vol 11:403–63 pp.Search in Google Scholar

21. Gazzolo, D, Bruschettini, M, Lituania, M, Serra, G, Bonacci, W, Michetti, F. Increased urinary S100B protein as an early indicator of intraventricular hemorrhage in preterm infants: correlation with the grade of hemorrhage. Clin Chem 2001;47:1836–8. https://doi.org/10.1093/clinchem/47.10.1836.Search in Google Scholar

22. Sannia, A, Zimmermann, LJI, Gavilanes, AWD, Vles, HJ, Serpero, LD, Frulio, R, et al.. S100B protein maternal and fetal bloodstreams gradient in healthy and small for gestational age pregnancies. Clin Chim Acta 2011;412:1337–40. https://doi.org/10.1016/j.cca.2011.03.034.Search in Google Scholar PubMed

23. Florio, P, Marinoni, E, Di Iorio, R, Bashir, M, Ciotti, S, Sacchi, R, et al.. Urinary S100B protein concentrations are increased in intrauterine growth-retarded newborns. Pediatrics 2006;118:e747–54. https://doi.org/10.1542/peds.2005-2875.Search in Google Scholar PubMed

24. Gazzolo, D, Marinoni, E, Di Iorio, R, Lituania, M, Bruschettini, PL, Michetti, F. Circulating S100β protein is increased in intrauterine growth-retarded fetuses. Pediatr Res 2002;51:215–9. https://doi.org/10.1203/00006450-200202000-00015.Search in Google Scholar PubMed

25. Gazzolo, D, Di Iorio, R, Marinoni, E, Masetti, P, Serra, G, Giovannini, L, et al.. S100B protein is increased in asphyxiated term infants developing intraventricular hemorrhage. Crit Care Med 2002;30:1356–60. https://doi.org/10.1097/00003246-200206000-00037.Search in Google Scholar PubMed

26. Michetti, F, D’Ambrosi, N, Toesca, A, Puglisi, MA, Serrano, A, Marchese, E, et al.. The S100B story: from biomarker to active factor in neural injury. J Neurochem 2019;148:168–87. https://doi.org/10.1111/jnc.14574.Search in Google Scholar PubMed

27. Giussani, DA, Thakor, AS, Frulio, R, Gazzolo, D. Acute hypoxia increases S100β protein in association with blood flow redistribution away from peripheral circulations in fetal sheep. Pediatr Res 2005;58:179–84. https://doi.org/10.1203/01.pdr.0000169999.66157.c0.Search in Google Scholar PubMed

28. Garnier, Y, Frigiola, A, Li Volti, G, Florio, P, Frulio, R, Berger, R, et al.. Increased maternal/fetal blood S100B levels following systemic endotoxin administration and periventricular white matter injury in preterm fetal sheep. Reprod Sci 2009;16:758–66. https://doi.org/10.1177/1933719109335801.Search in Google Scholar PubMed

29. Gazzolo, D, Pluchinotta, F, Bashir, M, Aboulgar, H, Said, HM, Iman, I, et al.. Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the “Cooperative Multitask against Brain Injury of Neonates” (CoMBINe) international study. PloS One 2015;10:e0115194. https://doi.org/10.1371/journal.pone.0115194.Search in Google Scholar PubMed PubMed Central

30. Gazzolo, D, Lituania, M, Bruschettini, M, Ciotti, S, Sacchi, R, Serra, G, et al.. S100B protein levels in saliva: correlation with gestational age in normal term and preterm newborns. Clin Biochem 2005;38:229–33. https://doi.org/10.1016/j.clinbiochem.2004.12.006.Search in Google Scholar PubMed

Received: 2021-03-04
Accepted: 2021-04-26
Published Online: 2021-05-19
Published in Print: 2021-08-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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