The Clinical and Diagnostic Utility of S100B in Preterm Newborns Laura D. Serpero, Francesca Pluchinotta, Diego Gazzolo PII: DOI: Reference:
S0009-8981(15)00100-X doi: 10.1016/j.cca.2015.02.028 CCA 13868
To appear in:
Clinica Chimica Acta
Received date: Revised date: Accepted date:
26 May 2014 6 February 2015 14 February 2015
Please cite this article as: Serpero Laura D., Pluchinotta Francesca, Gazzolo Diego, The Clinical and Diagnostic Utility of S100B in Preterm Newborns, Clinica Chimica Acta (2015), doi: 10.1016/j.cca.2015.02.028
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
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Journal: Clinica Chimica Acta R2
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The Clinical and Diagnostic Utility of S100B in Preterm Newborns
NU
SC R
Laura D. Serpero0 PhD, Francesca Pluchinotta1 MD, and Diego Gazzolo0* MD, PhD
Dept. of Maternal Fetal and Neonatal Medicine, C. Arrigo Children’s Hospital Alessandria, Italy;
1
Dept. of Pediatric Cardiovascular Surgery IRCCS San Donato Milanese Hospital, San Donato
MA
0
TE
D
Milanese, Italy.
AC
CE P
Key words: S100B, fetus, newborn, hypoxia, brain damage, congenital heart diseases
*Author for correspondence, proofs and reprints: Diego Gazzolo MD, Dept. of Maternal Fetal and Neonatal Medicine, C. Arrigo Children’s Hospital Spalto Marengo 46 I-15100 Alessandria, Italy Tel: +39 0131 207241 Fax: +39 0131 207268 E-mail: [email protected]
ACCEPTED MANUSCRIPT
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CE P
TE
IP SC R NU MA
D
Preterm newborn (PN) Weeks (w) Gestational age (GA) Birth-weight (BW) Central nervous system (CNS) Magnetic resonance imaging (MRI) Cerebrospinal fluid (CSF) Unconventional biological fluids (UBF) Positive predictive value (PPV) Negative predictive value (NPV) Perinatal asphyxia (PA) Congenital heart diseases (CHD) Intra-ventricular hemorrhage (IVH) Receiver operating characteristic (ROC) Multiple of median (MoM) Cardiopulmonary by-pass (CPB) Intra Uterine Growth Restriction (IUGR)
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Abbreviations
ACCEPTED MANUSCRIPT Abstract (199 words) Preterm birth is still the most important cause of perinatal mortality and morbidity. Follow-
T
up studies showed that the majority of neurological abnormalities during childhood are already
IP
present in the first week after birth. In this light, the knowledge of the timing of the insult and/or of
SC R
the contributing factors is of utmost relevance in order to avoid adverse neurological outcome. Notwithstanding, the considerable advances in perinatal clinical care and monitoring, the early detection of cases at risk for brain damage is still a challenge because, when radiological pictures
NU
are still negative, brain damage may be already at a subclinical stage, with symptoms hidden by
MA
therapeutic strategies. Thus, it could be very relevant to measure quantitative parameters, such as neuroproteins, able to detect subclinical lesions at a stage when routine brain monitoring procedures are still silent.
TE
D
In the last decade, the assay of the brain-specific protein S100B in different biological fluids proved useful information on brain function and damage in the perinatal period.
CE P
Therefore, the present study provides an overview of the most recent findings on S100B role
AC
as a reliable marker of brain development/damage in preterm high risk fetuses and newborns.
ACCEPTED MANUSCRIPT Preterm Newborn: Definition and Epidemiology Preterm newborns (PN) are defined by the World Health Organization as births occurring
T
before the completion of 37 weeks (w) of gestational age (GA) [1] and are further subdivided into
IP
extreme (
S0009-8981(15)00100-X doi: 10.1016/j.cca.2015.02.028 CCA 13868
To appear in:
Clinica Chimica Acta
Received date: Revised date: Accepted date:
26 May 2014 6 February 2015 14 February 2015
Please cite this article as: Serpero Laura D., Pluchinotta Francesca, Gazzolo Diego, The Clinical and Diagnostic Utility of S100B in Preterm Newborns, Clinica Chimica Acta (2015), doi: 10.1016/j.cca.2015.02.028
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
T
Journal: Clinica Chimica Acta R2
IP
The Clinical and Diagnostic Utility of S100B in Preterm Newborns
NU
SC R
Laura D. Serpero0 PhD, Francesca Pluchinotta1 MD, and Diego Gazzolo0* MD, PhD
Dept. of Maternal Fetal and Neonatal Medicine, C. Arrigo Children’s Hospital Alessandria, Italy;
1
Dept. of Pediatric Cardiovascular Surgery IRCCS San Donato Milanese Hospital, San Donato
MA
0
TE
D
Milanese, Italy.
AC
CE P
Key words: S100B, fetus, newborn, hypoxia, brain damage, congenital heart diseases
*Author for correspondence, proofs and reprints: Diego Gazzolo MD, Dept. of Maternal Fetal and Neonatal Medicine, C. Arrigo Children’s Hospital Spalto Marengo 46 I-15100 Alessandria, Italy Tel: +39 0131 207241 Fax: +39 0131 207268 E-mail: [email protected]
ACCEPTED MANUSCRIPT
AC
CE P
TE
IP SC R NU MA
D
Preterm newborn (PN) Weeks (w) Gestational age (GA) Birth-weight (BW) Central nervous system (CNS) Magnetic resonance imaging (MRI) Cerebrospinal fluid (CSF) Unconventional biological fluids (UBF) Positive predictive value (PPV) Negative predictive value (NPV) Perinatal asphyxia (PA) Congenital heart diseases (CHD) Intra-ventricular hemorrhage (IVH) Receiver operating characteristic (ROC) Multiple of median (MoM) Cardiopulmonary by-pass (CPB) Intra Uterine Growth Restriction (IUGR)
T
Abbreviations
ACCEPTED MANUSCRIPT Abstract (199 words) Preterm birth is still the most important cause of perinatal mortality and morbidity. Follow-
T
up studies showed that the majority of neurological abnormalities during childhood are already
IP
present in the first week after birth. In this light, the knowledge of the timing of the insult and/or of
SC R
the contributing factors is of utmost relevance in order to avoid adverse neurological outcome. Notwithstanding, the considerable advances in perinatal clinical care and monitoring, the early detection of cases at risk for brain damage is still a challenge because, when radiological pictures
NU
are still negative, brain damage may be already at a subclinical stage, with symptoms hidden by
MA
therapeutic strategies. Thus, it could be very relevant to measure quantitative parameters, such as neuroproteins, able to detect subclinical lesions at a stage when routine brain monitoring procedures are still silent.
TE
D
In the last decade, the assay of the brain-specific protein S100B in different biological fluids proved useful information on brain function and damage in the perinatal period.
CE P
Therefore, the present study provides an overview of the most recent findings on S100B role
AC
as a reliable marker of brain development/damage in preterm high risk fetuses and newborns.
ACCEPTED MANUSCRIPT Preterm Newborn: Definition and Epidemiology Preterm newborns (PN) are defined by the World Health Organization as births occurring
T
before the completion of 37 weeks (w) of gestational age (GA) [1] and are further subdivided into
IP
extreme (
