Brain-specific NSE and S-100 proteins in umbilical blood after normal delivery

Abstract

Background: To determine normal blood levels of brain-specific proteins S-100 and neuron specific enolase (NSE) in healthy newborns and their mothers following uncomplicated birth. Methods: Umbilical artery and vein blood and maternal venous blood was collected at 112 consecutive uncomplicated deliveries. Venous blood samples were taken from 18 of the neonates 3 days after birth. S-100 and NSE were analyzed quantitatively by double antibody immunoluminometric assay (Sangtec Medical AB, Sweden). Results: Compared with adults, healthy neonates had higher levels of both S-100 and NSE. For S-100, median levels (range) were 1.10 μg/l (0.38–5.50 μg/l) and 0.98 μg/l (0.43–2.70 μg/l) in umbilical artery and vein, respectively. For NSE, median levels (range) in umbilical artery blood and vein were 27 μg/l (10–140 μg/l) and 10.75 μg/l (8.80–≥200 μg/l) respectively. The maternal venous blood levels of both S-100 and NSE were significantly lower than in their infants. At 3 days of life, neonatal venous levels of the proteins were still high: S-100, 0.48–9.70 μg/l; NSE, 17–≥200 μg/l. In contrast to adults, haemolysis affected the S-100 levels in umbilical blood significantly. Conclusion: Concentrations of both S-100 and NSE in blood are greater in newborns after normal birth than in healthy adults. The higher levels in umbilical artery blood than in umbilical vein blood are consistent with a fetal origin of these proteins. High levels in venous blood at 3 days of life suggest that the high levels at birth are not related to the birth process but reflect a high activity of these proteins during fetal development.

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.