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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



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.


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.


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.


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


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.


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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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