Pro-inflammatory biomarkers and long term neurological outcomes in hypothermia plus melatonin treated asphyxiated newborns. A preliminary approach

Abstract

OBJECTIVE: To evaluate serum neuronal and inflammatory biomarkers in asphyxiated newborns treated with hypothermia alone or hypothermia plus melatonin, and whether biomarkers correlate with neurodevelopmental outcomes. DESIGN: A pilot multicentre, randomized, controlled, double blind clinical trial. 25 newborns were recruited. Neonatal neural biomarkers were measured in serum samples at hospital admission (T0), 24 h (T1), 72 hours (T2) and 7−10 days of age (T3). Neurodevelopmental scales were performed at 6 and 18 months. Treated patients received a daily dose of intravenous melatonin, for 3 days. RESULTS: In melatonin-treated group, lower plasma levels of GM-CSF, IL-2 and IL-13 at T1 were measured vs placebo-group. We also corroborated, at T2, lower concentrations of GM-CSF, as well as IL-7 and IL-13 at T3. Throughout the study period, we found a significant decrease in GM-CSF concentrations in the treatment group. We have also observed sustained decrease over time of GMCSF and inflammatory cytokines IL-2, IL-7 and IL-13 correlates with better neurodevelopmental outcomes at 6 and 18 months. CONCLUSIONS: In neonates affected by hypoxic-ischemic encephalopathy, the addition of iv melatonin to hypothermia therapy affects plasma biomarker concentration in the first week of life, with a high correlation with long-term neurological prognosis.