Dissertation committee:
Δημήτριος Ρίζος, Αναπλ. Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αικατερίνη Λυκερίδου, Καθηγήτρια, Τμήμα Μαιευτικής, ΠΑΔΑ
Νικολέττα Ιακωβίδου, Αναπλ. Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Θεοδώρα Μπούτσικου, Αναπλ. Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ζωή Ηλιοδρομίτη, Επίκ. Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Χριστίνα Νάνου, Επίκ. Καθηγήτρια, Τμήμα Μαιευτικής, ΠΑΔΑ
Αντιγόνη Σαραντάκη, Επίκ. Καθηγήτρια, Τμήμα Μαιευτικής, ΠΑΔΑ
Summary:
Introduction: Brain injury (BI) is an adverse perinatal outcome in premature neonates. Early detection of high-risk premature neonates for the development of BI is not possible for the time being. The prognostic value of many biochemical markers (BMs) has been investigated, but none is being used in clinical practice yet.
Aim: The aim of this study was to investigate the levels of BMs "glial fibrillary acidic protein (GFAP)" and "S100 calcium- binding protein B (S100B)", in the serum of premature neonates with gestational age (GA) less than 34 weeks, who developed BI and specifically periventricular leukomalacia or cerebral hemorrhage, of varying degrees, in relation to normal neonates (NN) of the same GA, during the first three days of life. Additionally, it was investigated the correlation of the levels of the above BMs with clinical, laboratory, radiological findings and the degree of BI. Finally, multiple perinatal factors were combined with the above BMs for the creation of a possible prognostic model for the early detection of high-risk neonates to develop BI or adverse perinatal outcome, such as neonatal death.
Material - Method: This is a prospective longitudinal case-control study, in which 96 premature neonates who met the inclusion criteria were involved in total. The neonates were admitted to a Neonatal Intensive Care Unit (NICU) of a Private Obstetrical-Gynecological Clinic of Athens. Of these, 29 developed BI, based on overall ultrasound findings until their discharge from the NICU (case group). Then they were matched one to one (1:1 fashion) with neonates who had normal brain ultrasound findings (control group). For the needs of the research, it was used the remaining unused serum of the neonates, which came from arterial or venous blood, from the scheduled daily laboratory tests,. The first blood sample was received at the admission to the NICU. Regarding perinatal factors, extensive data were collected from the obstetrical and neonatal history. Serum measurements of BMs were performed using ELISA method and the statistical analysis of the results was performed with the IBM SPSS statistics version 23 program.
Results: The comparison between NN and neonates with BI did not show statistically significant differences in maternal characteristics, therapeutic interventions in pregnant women or neonates, nor in total duration of neonatal stay in NICU. As far as neonatal characteristics are concerned, neonates with BI had a significantly lower pH and white blood cell count upon admission to NICU compared to NN. In addition, base deficit and lactic acid values at admission, as well as the incidence of seizures and death, were significantly higher in neonates with BI. Necrotizing enterocolitis, in contrast, was significantly more common in NN. There was no statistically significant difference in GFAP levels between the two groups, however, neonates with BI showed more frequent GFAP levels above the kit’s lower detection limit (0.056 ng/ml) and this trend was significantly different between the two groups in the first three days of life. Neonates with BI had a significantly higher S100B serum concentration in the first three days of life, which showed a decreasing trend over the days. Serum S100B on day 1 was the best predictor of adverse neonatal outcome, such as death or grade II-IV cerebral hemorrhage. At a cut-off of 10.51 ng/ml, the S100B serum gave 100% sensitivity and 93.9% specificity for predicting adverse neonatal outcome.
Conclusions: The efficacy of GFAP as an early ΒΜ for the development of BI in premature neonates appears to be limited. Probably the use of a more sensitive kit for serum GFAP in the future will highlight its potential prognostic role. Finally, larger prospective studies may give prominence to the predictive value of serum S100B and identify it as the first clinically useful BM for the early detection of high-risk premature neonates to develop BI.
Keywords:
Βiochemical markers, Premature neonates, Brain injury, Neonatal intensive care unit, Perinatal factors
