Supervisors info:
Λυκερίδου Αικατερίνη, Καθηγήτρια Μαιευτικής, ΠΑΔΑ
Ρίζος Δημήτριος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Μαστοράκος Γεώργιος, Καθηγητής Ενδοκρινολογίας, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Introduction: Α common adverse perinatal outcome of preterm birth is neonatal brain injury (NBΙ). Early detection of neonates considered to be of high-risk for NBI development, has not yet been achieved. Currently, many researchers have investigated the prognostic value of various biochemical markers regarding NBI, but for the time being none of them are applied in clinical practice. The combination of specialized supportive care, such as "neuroprotective care", with the clinical use of biomarkers, probably may contribute to the optimal neurodevelopmental outcomes of these neonates.
Aim: The aim of the present study was to investigate the levels of the biochemical marker "activin-A" in the serum of preterm neonates with gestational age (GA) <34 weeks, who developed various degrees of NBI, in the form of periventricular leukomalacia (PVL) or intraventricular haemorrhage (IVH) and were associated with normal neonates of the same GA, during the first three days of life. Besides, the correlation of activin-A levels with clinical, laboratory and radiological findings, as well as with the severity of NBI, was investigated. Finally, multiple perinatal risk factors were combined with activin-A to create a possible prognostic model for early detection of high-risk neonates for NBI or for adverse perinatal outcome, such as neonatal death.
Material - Method: The present study is a prospective case-control study, which included a total of 96 premature neonates admitted to the Neonatal Intensive Care Unit (NICU) of a private Obstetrics-Gynecology Clinic of Athens. The 29 of them developed NBI, according to the total ultrasound findings until their discharge from the NICU (case group). Subsequently, these neonates were matched in a 1:1 fashion with neonates who had normal findings in head ultrasound (control group). For the purposes of the present study the remaining serum of the neonates, after routine laboratory tests, was used. The serum was derived from peripheral arterial or venous blood, while the first blood sample was taken immediately after the neonate’s admission to NICU. Extensive data were collected from the obstetric and neonatal history in order to identify perinatal risk factors that may be associated with NBI. Finally, serum activin-A was measured by ELISA and the statistical analysis was done using the IBM SPSS statistics version 23.
Results: Regarding maternal characteristics, therapeutic interventions performed on pregnant women or their neonates, but also the total length of stay of the neonates in NICU, no statistically significant difference was observed between the two groups (case-control). In terms of neonatal characteristics, neonates who developed NBI appeared to have significantly lower pH and white blood cell count upon admission to NICU compared to normal neonates. Also, admission values of baseline deficit and lactic acid, as well as the incidence of seizures and death, were significantly higher in neonates with NBI. Necrotic enterocolitis, on the other hand, was significantly more common in normal neonates. Activin-A was significantly higher in neonates with NBI during the first and second day of life, while its concentration showed a downward trend over the days. Serum activin-A in the 1st and 2nd day of life was a predictor of adverse neonatal outcome, such as death or grade II-IV intraventricular hemorrhage. With a cut-off value of 0.61ng/ml, serum activin-A gave 100% sensitivity and 33.1% specificity for predicting adverse neonatal outcome, while with a cut-off value of 1.725ng/ml, serum activin-A gave sensitivity 29% and specificity 100%.
Conclusions: Activin-A is significantly higher in neonates with NBI from the first day of life, when ultrasound findings are still absent. Based on the ROC curve, it appears that the prognostic value of activin-A in the 2nd day of life is considered to be marginally fair in terms of the prognosis of neonates who will develop NBI. Probably, more extensive research in the future regarding this biomarker may highlight its possible prognostic value and establish it as a reliable biomarker for early detection of NBI. Finally, larger prospective studies examining simultaneously the effects of neuroprotective care and the clinical use of biomarkers are likely to feature important practices for the prevention or minimization of neurodevelopmental disorders in neonates.
Keywords:
Periventricular Leukomalacia, Intraventricular Hemorrhage, Hypoxic-Ischemic Encephalopathy, Brain Injury, Premature Neonate
