Brain-specific NSE and S-100 proteins in umbilical blood after normal delivery
Introduction
In neonates, subtle neurological damage is difficult to detect clinically. A biochemical brain-damage marker would be of great value for diagnosis and as a prognostic tool.
S-100 is a calcium-binding protein consisting of two monomers, α and β, existing in different combinations. S-100ββ is found in high concentrations in the glial cells of the central nervous system (CNS), where S-100αβ can also be found [1], [2], [3]. S-100αα exists in skeletal muscle, heart and kidney [4], [5], [6]. In this report, the term S-100 will be used for brain-specific S-100 with a β subunit.
Neuron specific enolase (NSE) is a dimeric cytoplasmic isoenzyme. It is one of several enolases and is found mainly in neuronal and neuroendocrine tissues [7], [8] but also in erythrocytes [9]. High concentrations of NSE have been found in serum samples with haemolysis, due to its presence in erythrocytes.
Studies on patients with neurological lesions have suggested a quantitative relationship between the degree of cell damage in the CNS and the concentrations of S-100 and NSE in cerebrospinal fluid (CSF) [10], [11].
Quantitative determination of S-100 and NSE in serum may be useful for prognostic purposes in minor head injury [12] and to monitor the course of states such as severe head injury, brain infarction [13], [14], [15] and neurological outcome after cardiac surgery in children [16] and adults [17].
In neonates, only a few studies on these proteins have been published. Lindberg et al. [16] studied S-100 levels before and after cardiac surgery in children up to 16 years of age. S-100 protein in serum was detected before surgery in all neonates and in some of the children up to the age of 8 years. They found the highest levels in neonates, lower between 1 month and 1 year, and lowest at ages above 1 year. They reported a significant correlation between the S-100 level in serum and the duration of circulatory bypass. In a study where NSE levels in CSF were correlated to hypoxic–ischaemic encephalopathy (HIE), Thornberg et al. [18] found that all neonates with a high concentration of NSE (49–200 μg/l) died or suffered permanent brain damage. Infants with mild HIE had low NSE levels (9–43 μg/l), while the group with moderate HIE had a wider variation in NSE levels, reflecting the variation in brain damage and outcome in this group.
Gazzolo et al. [19] studied premature infants and found S-100 to be a reliable index of brain distress.
The purpose of this study was to establish the normal range of S-100 and NSE concentrations in umbilical blood, both arterial and venous, in healthy babies born at term, using an immunoluminometric assay. Such reference values have not been available hitherto and are needed for studies of infants with suspected perinatal brain damage. The reason why we decided to analyse both S-100 and NSE is the fact that, theoretically, there is a possibility of differentiating between grey and white matter damage as S-100 is present mainly in glial cells and NSE mainly in neurons [8]. Neonates born by normal vaginal delivery were also compared to neonates born by caesarean section.
Section snippets
Material and methods
Blood samples were collected during 2 months in 1998 at the Department of Obstetrics and Gynecology, Lund University Hospital, which is a tertiary perinatal centre. The study was approved by the Ethical Committee of the Faculty of Medicine, University of Lund. Informed maternal consent was obtained before inclusion in the study.
To be eligible for the study, one had to have an uncomplicated singleton spontaneous cephalic vaginal delivery or elective caesarean section (ECS) in gestational week 37
Results
Of 112 umbilical blood specimens, 58 were haemolysed in arterial, venous or both samples, as observed by inspection. NSE (median) in haemolysed umbilical arterial blood was 100 μg/l (range 27–200 μg/l; n=60), umbilical vein blood 82 μg/l (18–≥200 μg/l; n=54) compared to 27 μg/l (range 10–140 μg/l; n=52) and 23 μg/l (8.80–92 μg/l; n=58) in non-haemolysed blood (Fig. 1). The S-100 levels in haemolysed cord artery blood had a median of 1.90 μg/l (range 0.75–16 μg/l; n=52) while non-haemolysed cord
Discussion
The finding of higher levels of S-100 and NSE in neonatal umbilical blood and in the venous blood at 3 days of age, than in the mothers, as well as the finding of higher levels in arterial than in venous umbilical blood, indicate an independent fetal production of these proteins. All the mothers had values of S-100 and NSE within the reference range of healthy adults.
High levels of both proteins were found at 3 days of age and in umbilical blood, regardless of mode of delivery. This, together
Acknowledgements
Laboratory assistant Susanne Jörning for technical assistance.
AB Sangtec Medical for providing immunoluminometric assays for protein quantification.
This research was supported by the Medical Faculty, Lund University.
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